SCFTIR1/AFB-Based Auxin Perception

12 Pages·2015·0.52 MB·English

ThePlantCell,Vol.27:9–19,January2015,www.plantcell.orgã2015AmericanSocietyofPlantBiologists.Allrightsreserved.
REVIEW
SCFTIR1/AFB-Based Auxin Perception: Mechanism and Role in
Plant Growth and Development
MohammadSalehin,RammyaniBagchi,andMarkEstelle1
HowardHughesMedicalInstituteandSectionofCellandDevelopmentalBiology,UniversityofCaliforniaSanDiego,LaJolla,
California92093
Auxinregulatesavastarrayofgrowthanddevelopmentalprocessesthroughoutthelifecycleofplants.Auxinresponsesare
highlycontextdependentandcaninvolvechangesincelldivision,cellexpansion,andcellfate.Thecomplexityoftheauxin
response is illustrated by the recent finding that the auxin-responsive gene set differs significantly between different cell
types in the root. Auxin regulation of transcription involves a core pathway consisting of the TIR1/AFB F-box proteins, the
Aux/IAAtranscriptionalrepressors,andtheARFtranscriptionfactors.Auxinisperceivedbyatransientcoreceptorcomplex
consistingofaTIR1/AFBproteinandanAux/IAAprotein.AuxinbindingtothecoreceptorresultsindegradationoftheAux/
IAAsandderepressionofARF-basedtranscription.Althoughthebasicoutlinesofthispathwayarenowwellestablished,it
remainsunclearhowspecificityofthepathwayisconferred.However,recentresults,focusingonthewaysthatthesethree
familiesofproteinsinteract,arestartingtoprovideimportantclues.
INTRODUCTION PROTEIN2A(SKP2A)(Juradoetal.,2010),andthenuclearSCFTIR1/
AFBs-Aux/IAA(SKP-Cullin-Fbox[SCF],TIR1/AFB[TRANSPORTIN-
ThetermauxinisderivedfromtheGreekword“auxein,”which
HIBITORRESISTANT1/AUXINSIGNALINGF-BOX],AUXIN/INDOLE
meanstogrow.Darwinobservedtheeffectsofauxininplantsas
ACETICACID)auxincoreceptors(Dharmasirietal.,2005a;Kepinski
earlyas1880.Inhisbook“ThePowerofMovementinPlants,”he
and Leyser, 2005; Calderón-Villalobos et al., 2012). Although there
described how the effects of light on movement of canary grass
havebeensomeimportantrecentadvancesinourunderstandingof
coleoptiles were mediated by a chemical signal (Darwin and
ABP1,thisreviewfocusesontheSCFTIR1/AFBcomplexesandtheir
Darwin,1880).Ittookanother60yearsofresearchtoshowthat
function in auxin perception and the regulation of transcription in
this chemical signal is indole-3-acetic acid, the major naturally
Arabidopsisthaliana.
occurring auxin in plants (Haagen-Smit et al., 1946; Mauseth,
1991;Ravenetal.,1992;SalisburyandRoss,1992;Arteca,1996).
Afterthisdiscovery,auxinresearchadvancedrapidlyalongmul- SCFTIR1/AFBsANDAUXINPERCEPTION
tiple trajectories. Numerous auxinic compounds were identified,
some of which were developed as herbicides and growth regu- Auxinregulatestranscriptionofauxin-responsivegenesthrough
lators(Sterlingetal.,1997;CobbandReade,2010).Basedonthe the action ofthe TIR1/AFBF-boxproteins, theAux/IAAtran-
chemicalstructuresofthesecompounds,thespatialfeaturesof scriptionalrepressors,andtheauxinresponsefactors(ARFs).The
a hypothetical auxin receptor were predicted (Thimman, 1977). Arabidopsisgenomeencodes6TIR1/AFBs,29Aux/IAAproteins,
Thismarkedthebeginningofwhatturnedouttobeanextended and23ARFs.Ingeneral,theAux/IAAsactbydirectlybindingtothe
searchfortheauxinreceptor. ARFsandrecruitingthecorepressorproteinTOPLESS(TPL)tothe
Auxin has been associated with embryogenesis (reviewed in chromatin(Figure1;Szemenyeietal.,2008;reviewedinGuilfoyle
Jürgens, 1995), tropic responses (Firn and Digby, 1980), organo- andHagen,2007,2012;MockaitisandEstelle,2008;Chapmanand
genesis (Li et al., 2005; De Smet et al., 2010), root development Estelle,2009;WangandEstelle,2014;Guilfoyle,2015).Degrada-
(reviewed in Benjamins and Scheres, 2008), shoot development tionoftheAux/IAArepressorsisacriticaleventinauxinsignaling
(Vernoux et al., 2011), and plant defense (reviewed in Kazan and andrequiresaubiquitinproteinligaseE3calledSCFTIR1/AFB(Gray
Manners, 2009). Understanding how auxin can regulate so many etal.,1999,2001;Ramosetal.,2001).Thesubstraterecognition
diverse physiological and developmental processes is an active subunitofthisE3,theF-boxproteinTIR1(orrelatedAFBprotein),
andexcitingareaofcurrentresearch. wasfirstidentifiedinageneticscreenforauxintransportinhibitor-
Therearethreeknownclassesofauxinreceptors:AUXINBIND- responsemutants(Rueggeretal.,1998).Sincethen,anumberof
INGPROTEIN1(ABP1)(Herteletal.,1972;Jonesetal.,1998;Tromas elegantstudieshaveshownthatauxinpromotesdegradationofthe
et al., 2013; Xu et al., 2014), S-PHASE KINASE-ASSOCIATED Aux/IAA proteins through the SCFTIR1/AFB, in an auxin-dependent
manner (Gray et al., 2001; Dharmasiri et al., 2005a; Kepinski and
Leyser,2005;Tanetal.,2007).TheAux/IAAdegronislocatedina
[email protected]. conserveddomaincalledDomainII(dII).Insteadofcausingasub-
www.plantcell.org/cgi/doi/10.1105/tpc.114.133744 stratemodification,commonlyrequiredforsubstraterecognitionby
10 ThePlantCell
Figure1. SCFTIR1/AFB-BasedAuxinPerceptionandResponse.
(A) Domain structure of the Aux/IAA and ARF proteins. EAR is the ETHYLENE RESPONSE FACTOR-associated amphiphilic repression motif that
interactswiththeTPLcorepressor.ThedIIdomainfacilitatesinteractionwiththeTIR1/AFBproteininresponsetoauxin.ThePB1domainhasboth
positiveandnegativeelectrostaticinterfacesfordirectionalproteininteraction.DBDistheB3DNAbindingdomain,andMRisthemiddleregionthat
determinestheactivityoftheARF.
(B)ActivatingARFscanformdimersthroughtheirDBDsandbindinvertedrepeatAuxREs(Boeretal.,2014).Atlowauxinlevels,theAux/IAAproteins
formmultimerswithARFsandrecruitTPLtothechromatin.NotethatmostAuxREsarenotfoundasinvertedrepeatsinplantgenomes,indicatingthat
ARFsbindtoDNAinconfigurationsotherthanshownhere.
(C) High levels of auxin promote ubiquitination and degradation of Aux/IAAs through SCFTIR1/AFB and the proteasome. ARFs are free to activate
transcriptionoftargetgenes.ThesiteofAux/IAAubiquitinationisarbitrary.Theactualsitesareunknown.Auxinisrepresentedbytheredoval.
manyothercullin-basedE3ligases,auxinenhancestheinteraction SinglemutantsinmembersoftheTIR1/AFBgenefamilyhave,
betweenSCFTIR1/AFBandthedIIbydirectlybindingtoTIR1,dem- atmost,amildauxin-relatedphenotype.Thetir1mutantisauxin
onstratingthatTIR1isthelong-soughtauxinreceptor(Dharmasiri resistant and is slightly shorter than wild-type plants (Ruegger
etal.,2005a,Kepinskiand Leyser2005;reviewedin Skaaretal., etal.,1998).However,higherordermutantswithcombinations
2013). of afb1, afb2, and afb3 in the tir1 mutant background exhibit
SCFTIR1/AFB-BasedAuxinPerception 11
severegrowthdefectsandincreasedauxinresistance.Mostofthe
quadruple tir1 afb1 afb2 afb3 mutants arrest after germination.
Occasionally,tir1afb1afb2afb3plantsareabletogrowbeyondthis
stage but show defects in multiple auxin responses (Dharmasiri
etal.,2005b,Parryetal.,2009).Inaddition,mutationsinotherSCF
subunitslikeCUL1,ASK1,andRBX1causeauxinresistanceand
stabilize the Aux/IAA proteins (Gray et al., 1999, 2001, 2002;
Hellmannetal.,2003;Moonetal.,2007;Gilkerson,etal.,2009).
Recently,twonewtir1mutantswereidentifiedinayeasttwo-hybrid-
basedscreen.Thetir1D170Eandtir1M473Lmutationsincreasethe
affinityofTIR1fortheAux/IAAproteins,whereasplantsexpressing
tir1D170Eandtir1M473Ltransgenesshowanauxinhypersensitive
phenotypeanddevelopmentaldefects(Yuetal.,2013).
STRUCTURALINSIGHTINTOAUXINPERCEPTION
BYSCFTIR1/AFBs
All six members of the TIR1/AFB family have been shown to
functionasauxinreceptors(Dharmasirietal.,2005a,2005b;Parry
et al., 2009; Greenham et al., 2011). Besides the F-box domain,
theseproteinsalsocontainaleucine-richrepeat(LRR)domainwith
18 LRRs. AFB4 and AFB5 proteins are distinct from the other
members of this family in thatthey haveanN-terminalextension
thatisnotpresentinTIR1andAFB1toAFB3.
When the TIR1/AFB proteins were first shown to function as
auxinreceptors,themechanismofauxinperceptionwasunknown.
Later,structuralstudiesrevealedtheelegantwaythatauxinactsto
facilitatetheinteractionbetweenTIR1andtheAux/IAAsubstrate.
Figure2. StructureofTIR1-ASK1inaComplexwithIAAandtheDegron
ThestructureofTIR1wassolvedinacomplexwithASK1,thedII
PeptidefromIAA7.
peptide from the Aux/IAA IAA7, and auxin (Tan et al., 2007; re-
viewed in Calderon-Villalobos et al., 2010) (Figure 2). The TIR1- TIR1-ASK1 structure as described by Tan et al. (2007). ASK1 (green)
interactswithTIR1(red)throughtheF-boxdomain.IAA(blue)ispresent
ASK1 complexis mushroom shaped. Thecap of themushroom,
intheauxinbindingpocketandactstostabilizetheinteractionbetween
includingtheauxinbindingpocket,isformedbytheLRRdomainof
TIR1andthedegronpeptide(palecyan).AsingleInsP6molecule(pale
TIR1.TheF-boxdomaintogetherwithASK1formsthestemofthe
orange)isboundtoTIR1beneaththeauxinbindingpocket.
mushroom.TheLRRsformaslightlytwisted,incompletering-like
solenoidstructureofalternatingsolvent-facinga-helicesandcore-
liningb-strands.ThetopsurfaceoftheLRRdomainhasasingle The six TIR1/AFB proteins are part of small subclade of F-box
proteinswithsevenmembers.Theseventhproteininthefamilyis
pocket for auxin binding (Tan et al., 2007; reviewed in Calderon-
CORONATINEINSENSITIVE1(COI1),knowntobeessentialforthe
Villalobos et al., 2010). Strikingly, the structure of the TIR1-ASK1
response to jasmonic acid (JA), a hormone that is structurally un-
complex does not change substantially upon auxin binding, in-
related to auxin and has a very different role in the plant. Never-
dicatingthatauxindoesnotinduceaconformationalchange.Atthe
theless, there is a striking similarity between the auxin and JA
baseoftheauxinbindingpocketliesaninositolhexakisphosphate
(InsP6)molecule.AlthoughthebiologicalsignificanceofthisInsP6 signalingpathways(Chinietal.,2007;Thinesetal.,2007;Yanetal.,
2007;reviewedinKatsiretal.,2008;PérezandGoossens,2013).In
moleculeisnotknown,ithasbeensuggestedthatitmightactas
the case of JA, degradation of a family of repressors called the
astructuralcofactor(Tanetal.,2007).Structuralstudieswithdif-
JASMONATEZIM(JAZ)proteinsismediatedbyanE3ligasecalled
ferentauxincompoundsrevealedthatthebindingpocketforauxin
SCFCOI1. The interaction between the JAZ proteins and COI1 is
is somewhat promiscuous. Most importantly, these studies re-
mediatedbydirectbindingtotheJAderivativeJA-isoleucine(Thines
vealedthatunlikeanimalhormones,wheretheligandbindingsiteis
etal.,2007;Sheardetal.,2010).Thus,plantshaveevolvedasimilar
located distantfrom theactivesiteofthereceptor,auxinactsas
a“molecularglue”tostabilizetheinteractionbetweenTIR1andthe mechanismtorespondtoverydifferentregulatorymolecules.
Aux/IAAprotein(Tanetal.,2007;reviewed inCalderon-Villalobos
etal.,2010;Skaaretal.,2013).Sofar,thestructureofSCFTIR1has
THEAUXINCORECEPTORMODEL:ANEWWAYTO
beensolvedonlywiththeshortdegronsequencefromtheAux/IAA
THINKABOUTAUXINACTION
proteins(Tanetal.,2007).Itisexpectedthatacompletestructure
ofSCFTIR1withauxinandafull-lengthAux/IAAproteinwillreveal Recently, it was shown that efficient binding of auxin to TIR1
more structural insights into how auxin triggers ubiquitination of requirestheassemblyofacoreceptorcomplexconsistingofTIR1
Aux/IAAproteins. andanAux/IAAprotein(Calderón-Villalobosetal.,2012).Thismay
12 ThePlantCell
besignificantbecausetherearesixTIR1/AFBproteinsand29Aux/ Aux/IAAANDARFGENESACTDOWNSTREAM
IAAproteinsinArabidopsis.Thus,itispossiblethatdifferentcom- OFSCFTIR1/AFBs
binationsofTIR1/AFBandAux/IAAwillhavedifferentbiochemical
properties(Figure3).Indeed,auxinbindingassayswithpurifiedTIR1 The Aux/IAA genes were discovered because some members
arerapidlyinducedbyauxin.Inpea(Pisumsativum)andsoybean
andAux/IAAproteinsshowedthatdifferentcoreceptorcomplexes
have different affinities for auxin (Calderón-Villalobos et al., 2012). (Glycine max), the level of several Aux/IAA transcripts increased
withinafewminutesofauxintreatment(AbelandTheologis,1996;
Forexample,theTIR1-IAA7pairhasaK of10to15nMforIAA,
d reviewed in Hagen and Guilfoyle, 2002). It is important to note,
whileTIR1-IAA12hasaK ofbetween250and300nMforIAA.
d however, that some Aux/IAAs, like IAA28 in Arabidopsis, are not
DifferencesinK appeartobedeterminedprimarilybythedIIse-
d
auxininduced(Roggetal.,2001).
quenceof the Aux/IAAproteins, although other sequences may
Most of the Aux/IAA proteins have four conserved domains.
alsocontribute(Calderón-Villalobosetal.,2012).
Domain I has an ETHYLENE RESPONSE FACTOR ASSOCI-
Localizedregulationofauxinlevelshasakeyroleinanumberof
ATEDAMPHIPHILICREPRESSION(EAR)motifwheretheTPL/
processesincludingpositioningoforganprimordia,maintenanceof
TOPLESS RELATED corepressor binds (Long et al., 2006;
stemcellniches,patterningofthefruit,andabilityofauxintodirect
Szemenyeietal.,2008;Causieretal.,2012).DomainIIcontains
cell division, expansion, and differentiation (Jones et al., 1998;
thedegronsequence,whichinteractsdirectlywiththeTIR1/AFB
Sabatinietal.,1999;Reinhardtetal.,2000;Benkováetal.,2003;Li
et al., 2005; Sorefan et al., 2009; Jurado et al., 2010; Mähönen proteinandauxin.DomainIIIandDomainIVareresponsiblefor
et al., 2014). In the root, direct measurement of auxin levels in dimerizationwithotherAux/IAAproteinsandheterodimerization
differentcelltypes,aswellasthebehaviorofauxinreporters,in- withARFproteins(Ulmasovetal.,1997a).
dicate that auxin levels range widely with anauxin maximum Important insights into the roles of the Aux/IAA genes came
around thequiescentcenteranddecreasing auxinlevelsmoving from genetic studies. Gain-of-function mutations in several of
proximallyfromthequiescentcenteraswellasdistallytowardthe these genes, including IAA1/AXR5, IAA3/SHY2, IAA7/AXR2,
roottip(Peterssonetal.,2009;Vernouxetal.,2011;Brunoudetal., IAA12/BDL,IAA14/SLR,IAA17/AXR3,IAA18/CRANE,IAA19/MSG,
2012;Bandetal.,2014).Recently,celltype-specificgenome-wide andIAA28,leadtostabilizationoftherespectiveproteinbecause
analysis of auxin responses in four different root cell types was theyarenotdegradedbySCFTIR1/AFBs(Rouseetal.,1998;Tianand
reported.Oneofthehighlightsofthisstudywasthatdifferentcell Reed, 1999; Nagpal et al., 2000; Rogg et al., 2001; Fukaki et al.,
typeshavebothdivergentandparalleltranscriptomicresponseto 2002;Tatematsuetal.,2004;Yangetal.,2004;Ueharaetal.,2008;
auxin(Bargmannetal.,2013).Thesestudieshighlightthepresence Ploenseetal.,2009).Thegain-of-functionmutationsareallwithin
ofanauxingradientintherootandthetranscriptionalcomplexity a stretchof fiveconserved amino acids in the dII.The mutations
ofauxinaction.Itispossiblethatdiverseauxincoreceptorsmaybe preventSCFTIR1/AFBsbindingresultinginstabilizationoftheprotein
necessarytointerpretthewiderangeofauxinlevelsthatexistin (Ramos et al., 2001; Dreher et al., 2006). On the other hand, the
theplant.Thus,thecoreceptormechanismcoulddramaticallyex- analysisofloss-of-functionmutantshassofarfailedtorevealro-
pandthedynamicrangeofauxinperception,potentiallyproviding bustmutantphenotypesinArabidopsis,suggestingextensivege-
apartialexplanationforhowauxincontrolssomanydifferentas- neticredundancyamongmembersofthefamily(Remingtonetal.,
pects of plant development (Calderón-Villalobos et al., 2012; Lee 2004;Overvoordeetal.,2005;reviewedinReed,2001).Thisisin
etal.,2014). contrasttothesituationintomato(Solanumlycopersicum)where
several loss-of-function alleles or antisense constructs produce
arobustphenotypesuggestingthatthereislessredundancyinthis
species (Wang et al., 2005; Chaabouni et al., 2009; Bassa et al.,
2012;Dengetal.,2012;Suetal.,2014).
The ARF proteins are B3-type transcription factors. Each of
the 23 ARFs in Arabidopsis have anN-terminal DNA binding do-
main(DBD)similartothatfoundinthetranscriptionfactorFUSCA3
(Ulmasov et al., 1995, 1997b; Luerssen et al., 1998; reviewed in
Liscum and Reed, 2002). The ARFs bind to auxin response ele-
ments(AuxREs),eachwiththecanonical6-bpTGTCTCsequence
inthepromotersofauxin-responsivegenes.Thefirstfourbasesin
the TGTCTC sequence are absolutely required for ARF binding,
while more variation is tolerated in the last two bases (Ulmasov
et al., 1997b, 1999a; Boer et al., 2014; reviewed in Guilfoyle and
Hagen,2007).
BasedonactivityinaprotoplastassaytheARFsaredivided
Figure 3. Different TIR1/AFB-AUX/1AA-ARF Modules May Regulate intoactivatorsandrepressors(reviewedinGuilfoyleandHagen,
DifferentDevelopmentalProcesses. 2012).ARF5,6,7,8,and19proteinshaveamiddleregionthatis
Gln (Q) rich and function as activators. All the rest, except for
SixTIR1/AFBcaninteractwiththe23differentAux/IAAscontainingthedIIto
form numerous coreceptor complexes. Each of the Aux/IAA may interact ARF23, have a middle region rich in serine, proline, or leucine/
with up to 19 ARFs containing Domains III/IV to regulate distinct sets of glycineandarethoughttoactasrepressors,althoughthishas
targetgenesthatcontroldifferentphysiologicalprocessesintheplant. notbeenexperimentallytestedforeverymemberofthisgroup.
SCFTIR1/AFB-BasedAuxinPerception 13
In addition, ARF3, 13, and 17 lack Domains III/IV. ARF23 con- studiesoftheAux/IAAproteins.Expressionofstabilizedforms
sists of a truncated DBD only. Although the ARFs have been of these proteins results in a strong auxin response defect.
classified as either activators or repressors, it is important to However,ifoneofthetwoPB1facesismutated,thisdefectis
notethattheirbehaviorintheplantmaybemuchmorecomplex. strongly ameliorated, implying that the formation of Aux/IAA
FortheactivatingARFs,aworkingmodelforARFregulationis multimersisrequiredforefficientrepression.Sofar,thiseffect
nowwellestablished(Figure1;reviewedinGuilfoyleandHagen, hasonlybeendemonstratedforIAA16,butseemslikelytobe
2007, 2012). At low auxin levels, these ARFs are bound to the general.Thesediscoveriesconstituteamajorrefinementofthe
Aux/IAA proteins, which recruit the TPL corepressor and other auxin-signaling model (Figure 1; Korasick et al., 2014; Nanao
associated chromatin modifying proteins via the EAR motif in etal.,2014).
DomainI,resultingintherepressionofauxin-responsivegenes Inadditiontointeractionsbetweenthemselves,theAux/IAAs
(Tiwari et al., 2001; Szemenyei et al., 2008). At higher auxin andARFshavealsobeenreportedtoregulateandberegulated
levels (Figure 1), Aux/IAAs are ubiquitinated and degraded via byothertranscriptionfactors.AMYBtranscriptionfactor,MYB77,
the 26S proteasome machinery, thus freeing ARFs to activate wasshowntointeractwiththeARF7proteinandcontributetoauxin-
expression of auxin responsive genes (Figure 1). Since the regulated transcription (Shin et al., 2007). In sunflower (Helianthus
phenotype of gain-of-function aux/iaa mutants is caused by annuus),HaIAA27wasshowntobindtotheheatshocktranscription
stabilizationoftherespectiveAux/IAAproteinsandconstitutive factorHaHSFA9andrepressitsactivityduringseeddevelopment.
repression ofARF proteins, loss-of-function ARF activator mu- AsinthecaseoftheARFs,auxinactedtorelieverepressionofthe
tantsshouldhaveasimilarphenotypetoAux/IAAgain-of-function HaHSFA9protein(Carrancoet al.,2010).In anotherrecentreport,
mutants.Thisisthecaseforseveralmutants,suchasiaa12/bdland phosphorylation of ARF7 and ARF19 by BRASSINOSTEROID IN-
arf5/mp, both of which have a rootless phenotype (Hardtke and SENSITIVE2 (BIN2) was shown to suppress their interaction with
Berleth,1998;Hamannetal.,1999;Weijersetal.,2006). Aux/IAAsandthisinturnenhancedtranscriptionofLATERALOR-
Recently,alarge-scaleanalysisofAux/IAAandARFsinterac- GANBOUNDARIESDOMAIN16(LBD16)andLBD29duringlateral
tionswasdoneusingsystemiclarge-scaleyeasttwo-hybridassays rootinitiation,independentofauxinperception(Choetal.,2014).
andbimolecularfluorescencecomplementationassays.Themajor Despitetheserecentadvances,ourunderstandingofhowthe
conclusionofthisstudywasthatAux/IAA-Aux/IAAandAux/IAA- ARFs work remains quite superficial compared with fungal and
activatorARFinteractionsarecommon,whereasinteractionsbe- animalsystems.Forexample,wearejustbeginningtolearnabout
tweenARFsorbetweenAux/IAAsandrepressorARFswereless thecoactivatorsandcorepressorsthatcollaboratewiththeARFsto
common(Vernouxetal.,2011).However,arecentstudyprovides regulate transcription. Similarly, the chromatin states associated
genetic evidence for an interaction between ARF9, characterized withARFfunctionareunknown.Finally,thefunctionandactivityof
as a repressor, and IAA10, suggesting either the function of the therepressorARFsispoorlyunderstood.
ARFsismorecomplexorthattheAux/IAAscaninteractwithre-
pressorARFsinvivo(Rademacheretal.,2012).
DEGRADATIONOFAux/IAAISCRUCIALFOR
Recent structural studies of ARFs have led to exciting new
AUXINACTION
insightintothemolecularfunctionoftheARFandAux/IAAproteins
(Boer et al., 2014; Korasick et al., 2014; Nanao et al., 2014). Be- Understanding how Aux/IAA proteins are degraded is a crucial
causetheARFproteinsreadilyformhomodimersthroughDomains step in unraveling how auxin triggers diverse developmental
III/IV,thisbecamethefocusofstudiesonARFinteraction.However responses.DomainIIoftheAux/IAAsisthoughttobetheprimary
DomainIII/IV-independentARFdimerizationwasreportedaslong determinant for degradation by SCFTIR1/AFB (Gray et al., 2001;
ago as 1999 (Ulmasov et al., 1999b). More recently, Boer et al. Ramosetal.,2001;Dreheretal.,2006).However,inadditiontothe
(2014)solvedthestructureoftheDNAbindingdomainsfromARF5 DomainIIdegronmotif,aconservedlysinebetweenDomainIand
anditsdistantparalogARF1incomplexwithagenericAuxREel- DomainIIcontributestoAux/IAAdegradation(Ouelletetal.,2001;
ementandshowedthattheDNAbindingdomainshomodimerizeto Dreheretal.,2006).Itisinterestingtonotethatthehalf-lifeofthe
generatecooperativeDNAbinding(Boeretal.,2014).Furthermore, Aux/IAAsvarieswidely.Thehalf-lifeofIAA7is;10min,whilethe
this study proposed that ARF1 and ARF5 differ in the spacing half-lifeofIAA28is80min,despitethefactthatthesetwoproteins
between adjacent binding sites, potentially contributing to ARF have an identical degron sequence. These results indicate that
specificity. determinants outside of Domain II also contribute to degradation
FurtherinsightwasgainedbystructuralstudiesoftheC-terminal rate.Ontheotherhand,IAA31,whichhasadegenerateDomainII,
domain of ARF5 (Nanao et al., 2014) and ARF7 (Korasick et al., withouttheconservedlysine,hasahalf-lifeof>20h,althoughthis
2014).ThisworkrevealedthatDomainsIIIandIV,presentinmost drops to ;4 h after auxin treatment. A small group of Aux/IAAs,
oftheAux/IAAandARFs,formaPhoxandBem1p(PB1)domain namely, IAA20, IAA30, and IAA32-34, do not have the classical
asfirstproposedbyGuilfoyleandHagen(2012).ThePB1domains Domain II, but overexpression of IAA20 and IAA30 show strong
provide both positive and negative electrostatic surfaces for di- auxin-related defects implying that these proteins repress auxin
rectional protein interaction (reviewed in Guilfoyle, 2015).Bio- regulatedtranscription(SatoandYamamoto,2008).
chemicalanalysisconfirmedthatamutationthataffectsoneor Recently, a synthetic biology approach has been applied to
the other of the surfaces in the ARF protein still permits dimeri- thestudyofauxinsignaling(Havensetal.,2012;Pierre-Jerome
zation withitselforanAux/IAAprotein, whereas an ARF protein etal.,2014).Byengineeringthecoreauxin-signalingpathwayinto
withsubstitutionsinbothfacesisunabletoformadimer(Korasick budding yeast, these workers developed a novel and powerful
etal.,2014;Nanaoetal.,2014).Additionalinsightwasgainedby platform for studies of the pathway. Using this system, they
14 ThePlantCell
confirmedthattheAux/IAAproteinsaredegradedatverydifferent
rates, but in addition, the rate is dependent on the TIR1/AFB
protein (Havens et al., 2012). More importantly, the system en-
abledthemtodefineaminimalauxinresponsecircuitsufficientto
recapitulateauxin-inducedtranscriptioninyeast.Bybuildingand
testingcircuitscomposedofdifferentAux/IAAandARFproteins,
they were able to show that the behavior of the circuit varied
significantlydepending on thecircuitcomponents.Furthermore,
circuits with multiple coexpressed Aux/IAAs displayed unique
behaviors that may be relevant during plant development. This
workprovidesanewapproachfordissectingauxinsignalingand
demonstrates the key role of Aux/IAAs in tuning the dynamic
patternofauxinresponse(Pierre-Jeromeetal.,2014).
Inarelatedstudy,Shimizu-MitaoandKakimoto(2014)tested
theauxin-dependentdegradationofallArabidopsisAux/IAAsin
combinationwithTIR1orAFBinyeast.TheyfoundthatTIR1and
AFB2,butnotAFB1,orAFB3-5wereeffectiveinAux/IAAdegra-
dation in the yeast system. All Aux/IAAs, except those lacking
DomainII(IAA20,IAA30,IAA32,andIAA34),weredegradedinan
auxin-dependentmanner.Asinearlierstudies(Calderón-Villalobos
et al., 2012),theeffective auxin concentration for Aux/IAA degra-
dation depended on the identity of both the Aux/IAA and TIR1/
AFB2protein(Shimizu-MitaoandKakimoto,2014).
Figure4. RegulationoftheTIR1/AFBPathway.
ARF-mediated regulation of the Aux/IAA genes constitutes a robust
REGULATORYLOOPSINAUXINSIGNALING
negative feedback loop. Other pathways may regulate transcription of
auxinresponsegenesinbothapositiveandnegativemanner.Forex-
Regulatorycomplexityisarecurringthemeinplantdevelopment,
ample, the cytokinin responsive transcription factor ARR1 promotes
soitisnotsurprisingthatfeedbackandregulatoryloopsexistinthe
transcriptionofIAA3intheroot,resultingindownregulationoftheARF
auxin-signalingpathway(Figure4).Themoststrikingoftheseisthe
targetPIN1.Thisresultsinachangeinauxindistributionthataffectscell
negative feedback loop generated by auxin-induced transcription differentiation(DelloIoioetal.,2008).Inaddition,otherpathwaysmay
oftheAux/IAAgenes.Clearlythisfeedbackloopwillresultinrapid act directly on the ARFs. For example, the BIN2 kinase regulates the
dampening of auxin response upon auxin treatment. However, interactionbetweenARF7andAux/IAAbydirectlyphosphorylatingthe
giventhatthekineticsofauxinregulationofAux/IAAsiscomplex, ARF(Choetal.,2014).
a complete understanding of this regulatory system will require
additionalexperimentsinconjunctionwithamodelingapproach.
Itislikelythatmanyadditionalregulatorynodesthatinvolvethe
Apart from the negative regulatory loop involving the Aux/
IAAs, members of the auxin efflux carrier PIN-FORMED (PIN) Aux/IAAsandARFwillbeidentifiedgoingforward(Figure4).
familywerealsoshowntobeundercontroloftheAux/IAAsand
ARFs(Vietenetal.,2005).Ascellularauxinlevelsrise,PINgene
THEEVOLUTIONARYHISTORYOFAUXINSIGNALING
expressionincreases,resultinginmoreauxineffluxandareduction
inauxinlevels(reviewedinAdamowskiandFriml,2015).Thus,this Colonization of land by plants was a major event in evolution.
regulatory circuit contributes to auxin homeostasis. Among the However,thetimeatwhichauxinsignalingemergedisnotclear
features of this regulation is a striking compensatory mechanism (reviewedinDeSmetandBeeckman,2011).Theauxin-signaling
thatmayacttostabilizeauxingradients.Inthissystem,thelossof pathwayisconservedinlandplants.GenesencodingAux/IAA,
aPINproteinresultsinanincreaseincellularauxinlevels.Thisin ARF, and TIR1 homologs are present within the genomes of
turn causes the ectopic expression of other PIN proteins, thus themossPhyscomitrellapatensandthelycophyteSelaginella
compensatingfortheoriginalPINdeficiency(Vietenetal.,2005).In moellendorffii(Lauetal.,2009;Paponovetal.,2009;reviewedin
addition, accumulation of auxin during de novo organ formation De Smetand Beeckman, 2011;Finet and Jaillais, 2012).In the
leadstorearrangementsinthesubcellularpolarlocalizationofPIN case of P. patens, genetic studies have shown that the mech-
auxintransporters.Thiseffectiscellspecific,independentofPIN anism of auxin signaling is very similar to that of angiosperms
transcription, and involves the Aux/IAA-ARF signaling pathway (Priggeetal.,2010;Lavyetal.,2012).Thepresenceofauxinin
(Saueretal.,2006). algal species has been reported, but the physiological signifi-
ThePINsalsofactorintoanotherauxin-dependentregulatory canceofthisisnotclear.InthecaseofChlorophyta,adivisionof
loopthataffectsbehaviorofcellsintherootmeristem.DelloIoio the green algae, no orthologs of TIR1/AFB, Aux/IAA, and ARFs
et al. (2008) showed that the cytokinin response factor ARR1 werefound(Paponovetal.,2009;reviewedinLauetal.,2009;De
activates transcription of the Aux/IAA gene SHY2/IAA3. The Smet and Beeckman, 2011; Finet and Jaillais, 2012). A recent
IAA3proteininturnrepressestranscriptionofPIN1resultingin reportofa draft genome sequence of thefilamentous terrestrial
achangeinauxindistributionthatpromotescelldifferentiation. alga Klebsormidium flaccidum indicates that this species lacks
SCFTIR1/AFB-BasedAuxinPerception 15
aTIR1-likeauxinreceptorbutdoeshaveotherauxin-relatedpro- phyllotaxy,lateralbranching,androotgrowth(Reinhardtetal.,2003;
teins such as ABP1, AUXIN RESISTANT1, and PIN (Hori et al., Jönsson et al., 2006; Shinohara et al., 2013; Band et al., 2014;
2014).ItisalsointerestingtonotethatmostoftheSCF-dependent Mähönenetal.,2014).Thisinsightfulapproachwillbecomeeven
planthormonesignalingcomponents,suchasTIR1,COI1,andGA morepowerfulasthemodelsbecomeincreasinglyparameterized
INSENSITIVEDWARF1,aremissinginK.flaccidumgenome(Hori byexperimentaldata.
etal.,2014).
FUTUREDIRECTIONS
USEOFAUXIN-INDUCIBLEDEGRONSASATOOLIN
Auxin plays a role almost every aspect of plant development.
ANIMALSYSTEMS
Although the general framework of auxin action has been estab-
In the last several years, SCFTIR1/AFB and the Aux/IAA proteins lished,thespecificelementsinvolvedineachdevelopmentalsignal
remaintobediscovered.BecausetheAux/IAAproteinsarecentral
haveprovidedthebasisforanovelmethodofregulatingprotein
and dynamicregulatorsofauxinsignaling,furtherstudiesoftheir
levels in non-plant species. This system is called the auxin-
role in auxin perception, their interactions with the ARF proteins,
inducibledegronsystem(Nishimuraetal.,2009;Hollandetal.,
and their ultimate effect on the transcriptional output will be an
2012;Kankeetal.,2012;Farretal.,2014;NishimuraandKanemaki,
important way forward. The ability of the Aux/IAAs to form auxin
2014;Samejimaetal.,2014).AlleukaryotespossessSCFubiquitin
coreceptorswithTIR1/AFBsfurtherexpandsthedynamicrangeof
ligases, and the architecture of Arabidopsis TIR1, including the
F-box domain,is sufficiently conserved to allow assembly into an auxin perception. In addition, recent exciting studies show that
SCFTIR1complexinyeastandanimals.Whenaproteinofinterestis ABP1functionsasacellsurface-basedauxinreceptor(Chenetal.,
2001;Chenetal.,2012;Xuetal.,2014).Howauxinperceptionat
fusedtotheAux/IAAdegron,calledtheauxin-induceddegroninthis
thecellsurfaceandinthenucleusarecoordinatedisanimportant
context,andintroducedintoyeastcellsexpressingTIR1,thetagged
outstandingquestion(Tromasetal.,2013;Paqueetal.,2014).Fi-
proteinwillbedegradedinanauxin-dependentmanner(Nishimura
nally,theeffectsofauxinoncellcycleregulationmaybemediated
et al., 2009). The system provides a rapid and, more importantly,
in part by SCFSKP2A, which binds to auxin in a cell-free assay
reversiblewaytoregulateproteinlevels.Theauxin-inducibledegron
(Juradoetal.,2010).Discoveringhowinformationfromthesedif-
systemhasbeenadaptedforanumberofvertebratecelltypesand
ferent perception mechanisms is integrated during plant de-
isprovingtobeausefultoolforawiderangeofstudies
velopmentwillbeanexcitingchallengeforthefuture.
NEWTECHNOLOGIESTODISSECTTHE
ACKNOWLEDGMENTS
AUXIN-SIGNALINGPATHWAY
M.S.andR.B.thankRebeccaDicksteinforcriticallyreadingthearticle
Asmentionedabove,thereappearstobeextensiveredundancy
andforhelpfulsuggestions.Thisworkwassupportedbygrantsfromthe
inboththeARFandAux/IAAfamiliesofproteins.Consequently,
HowardHughesMedicalInstitute,theGordonandBettyMooreFounda-
theroleofeachAux/IAAandARFproteinhasnotbeendefined
tion,andtheNationalInstitutesofHealth(GrantGM43644).
(Okushima et al., 2005; Overvoorde et al., 2005). Because the
creationofhigherordermutants bygeneticcrossingisatime-
consuming process, the emergence of precise genome editing AUTHORCONTRIBUTIONS
tools like CLUSTERED REGULARLY INTERSPACED SHORT
Allauthorscontributedtowritingthearticle.
PALINDROMICREPEAT(CRISPR)-CRISPRASSOCIATEDSYSTEM
(Cas9)isawelcomedevelopment(Congetal.,2013;Malietal.,
2013). The CRISPR-Cas9 system has been successfully used
Received October 29, 2014; revised December 14, 2014; accepted
to create multiple mutants in a mouse model in a short time
December26,2014;publishedJanuary20,2015.
(Wang et al., 2013). Several reports of successful precise ge-
nome editing in Arabidopsis and other plants using CRISPR-
Cas9areverypromising(Lietal.,2013;Fengetal.,2014;Jiang
REFERENCES
etal.,2014;Schimletal.,2014;reviewedinLozano-Justeand
Cutler, 2014; Hyun et al., 2015). The CRISPR-Cas9 system Abel, S., and Theologis, A. (1996). Early genes and auxin action.
should decrease the amount of time it takes to generate the PlantPhysiol.111:9–17.
higherordermutantsrequiredforanalysisofAux/IAAandARF Adamowski, M., and Friml, J. (2015). PIN-dependent auxin transport:
genefamilies. action,regulation,andevolution.PlantCell27:20–32.
Overthelastthreedecadesgenetics,biochemistryandmolec- Arteca,R.(1996).PlantGrowthSubstances:PrinciplesandApplica-
tions.(NewYork:Chapman&Hall).
ular approaches have provided an explanation for how auxin
Band, L.R.,etal. (2014). Systems analysis of auxin transportin the
controlsmanyaspectsofplantgrowth.However,partlybecauseof
Arabidopsisrootapex.PlantCell26:862–875.
thecomplexityofauxinbiology,ourviewofthisregulatorysystem
Bargmann,B.O.R.,Vanneste,S.,Krouk,G.,Nawy,T.,Efroni,I.,Shani,E.,
remainsincomplete.Amorecompleteunderstandingwillcertainly
Choe,G.,Friml,J.,Bergmann,D.C.,Estelle,M.,andBirnbaum,K.D.
require the application of systems level and computational ap- (2013).Amapofcelltype-specificauxinresponses.Mol.Syst.Biol.9:688.
proaches.Severalgroupshavedevelopedinstructivemathematical Bassa,C.,Mila,I.,Bouzayen,M.,andAudran-Delalande,C.(2012).
models that help to explain several auxin-related events like Phenotypes associated with down-regulation of Sl-IAA27 support
16 ThePlantCell
functionaldiversityamongAux/IAAfamilymembersintomato.Plant Deng,W.,Yang,Y.,Ren,Z.,Audran-Delalande,C.,Mila,I.,Wang,
CellPhysiol.53:1583–1595. X.,Song,H.,Hu,Y.,Bouzayen,M.,andLi,Z.(2012).Thetomato
Benjamins, R., and Scheres, B. (2008). Auxin: the looping star in SlIAA15 is involved in trichome formation and axillary shoot de-
plantdevelopment.Annu.Rev.PlantBiol.59:443–465. velopment.NewPhytol.194:379–390.
Benková,E.,Michniewicz,M.,Sauer,M.,Teichmann,T.,Seifertová, De Smet, I., and Beeckman, T. (2011). Asymmetric cell division in
D., Jürgens, G., and Friml, J. (2003). Local, efflux-dependent auxin landplantsandalgae:thedrivingforcefordifferentiation.Nat.Rev.
gradients as a common module for plant organ formation. Cell 115: Mol.CellBiol.12:177–188.
591–602. DeSmet,I.,etal.(2010).Bimodularauxinresponsecontrolsorgan-
Boer, D.R., Freire-Rios, A., van den Berg, W.A.M., Saaki, T., ogenesis in Arabidopsis. Proc. Natl. Acad. Sci. USA 107: 2705–
Manfield, I.W., Kepinski, S., López-Vidrieo, I., Franco-Zorrilla, 2710.
J.M.,deVries,S.C.,Solano,R.,Weijers,D.,andColl,M.(2014). Dharmasiri,N.,Dharmasiri,S.,andEstelle,M.(2005a).TheF-box
StructuralbasisforDNAbindingspecificitybytheauxin-dependent proteinTIR1isanauxinreceptor.Nature435:441–445.
ARFtranscriptionfactors.Cell156:577–589. Dharmasiri,N.,Dharmasiri,S.,Weijers,D.,Lechner,E.,Yamada,
Brunoud, G., Wells, D.M., Oliva, M., Larrieu, A., Mirabet, V., M., Hobbie, L., Ehrismann, J.S., Jürgens, G., and Estelle, M.
Burrow, A.H., Beeckman, T., Kepinski, S., Traas, J., Bennett, (2005b). Plant development is regulated by a family of auxin re-
M.J., and Vernoux, T. (2012). A novel sensor to map auxin re- ceptorFboxproteins.Dev.Cell9:109–119.
sponseanddistributionathighspatio-temporalresolution.Nature Dreher, K.A., Brown, J., Saw, R.E., and Callis, J. (2006). The Ara-
482:103–106. bidopsisAux/IAAproteinfamilyhasdiversifiedindegradationand
Calderón Villalobos, L.I., et al. (2012). A combinatorial TIR1/AFB- auxinresponsiveness.PlantCell18:699–714.
Aux/IAA co-receptor system for differential sensing of auxin. Nat. Farr, C.J., Antoniou-Kourounioti, M., Mimmack, M.L., Volkov, A.,
Chem.Biol.8:477–485. and Porter, A.C. (2014). The a isoform of topoisomerase II is re-
Calderon-Villalobos,L.I.,Tan,X.,Zheng,N.,andEstelle,M.(2010). quired for hypercompaction of mitotic chromosomes in human
Auxinperception—structuralinsights.ColdSpringHarb.Perspect. cells.NucleicAcidsRes.42:4414–4426.
Biol.2:a005546. Feng, Z., et al. (2014). Multigeneration analysis reveals the in-
Carranco, R., Espinosa, J.M., Prieto-Dapena, P., Almoguera, C., heritance, specificity, and patterns of CRISPR/Cas-induced gene
andJordano,J.(2010).Repressionbyanauxin/indoleaceticacid modificationsinArabidopsis.Proc.Natl.Acad.Sci.USA111:4632–
protein connects auxin signaling with heat shock factor-mediated 4637.
seedlongevity.Proc.Natl.Acad.Sci.USA107:21908–21913. Finet,C.,andJaillais,Y.(2012).Auxology:whenauxinmeetsplant
Causier, B., Ashworth, M., Guo, W., and Davies, B. (2012). The evo-devo.Dev.Biol.369: 19–31.
TOPLESS interactome: a framework for gene repression in Arabi- Firn, R.D., and Digby, J.(1980). The establishment of tropic curva-
dopsis.PlantPhysiol.158:423–438. turesinplants.Annu.Rev.PlantPhysiol.31:131–148.
Chaabouni,S.,Jones,B.,Delalande,C.,Wang,H.,Li,Z.,Mila,I., Fukaki,H.,Tameda,S.,Masuda,H.,andTasaka,M.(2002).Lateral
Frasse, P., Latché, A., Pech, J.-C., and Bouzayen, M. (2009). root formation is blocked by a gain-of-function mutation in the
Sl-IAA3,atomatoAux/IAAatthecrossroadsofauxinandethylenesig- SOLITARY-ROOT/IAA14geneofArabidopsis.PlantJ.29:153–168.
nallinginvolvedindifferentialgrowth.J.Exp.Bot.60:1349–1362. Gilkerson,J.,Hu,J.,Brown,J.,Jones,A.,Sun,T.P.,andCallis,J.
Chapman, E.J., and Estelle, M. (2009). Mechanism of auxin-regu- (2009).Isolationandcharacterizationofcul1-7,arecessivealleleof
latedgeneexpressioninplants.Annu.Rev.Genet.43:265–285. CULLIN1thatdisruptsSCFfunctionattheCterminusofCUL1in
Chen, J.-G., Ullah, H., Young, J.C., Sussman, M.R., and Jones, Arabidopsisthaliana.Genetics181:945–963.
A.M.(2001).ABP1isrequiredfororganizedcellelongationanddivision Gray, W.M., del Pozo, J.C., Walker, L., Hobbie, L., Risseeuw, E.,
inArabidopsisembryogenesis.GenesDev.15:902–911. Banks,T.,Crosby,W.L.,Yang,M.,Ma,H.,andEstelle,M.(1999).
Chen, X., Naramoto, S., Robert, S., Tejos, R., Löfke, C., Lin, D., IdentificationofanSCFubiquitin-ligasecomplexrequiredforauxin
Yang,Z.,andFriml,J.(2012).ABP1andROP6GTPasesignaling responseinArabidopsisthaliana.GenesDev.13:1678–1691.
regulateclathrin-mediatedendocytosisinArabidopsisroots.Curr. Gray, W.M., Hellmann, H., Dharmasiri, S., and Estelle, M. (2002).
Biol.22:1326–1332. RoleoftheArabidopsisRING-H2proteinRBX1inRUBmodification
Chini, A., Fonseca, S., Fernández, G., Adie, B., Chico, J.M., andSCFfunction.PlantCell14:2137–2144.
Lorenzo, O., García-Casado, G., López-Vidriero, I., Lozano, F.M., Gray, W.M., Kepinski, S., Rouse, D., Leyser, O., and Estelle, M.
Ponce,M.R.,Micol,J.L.,andSolano,R.(2007).TheJAZfamilyofre- (2001).AuxinregulatesSCF(TIR1)-dependentdegradationofAUX/
pressorsisthemissinglinkinjasmonatesignalling.Nature448:666–671. IAAproteins.Nature414:271–276.
Cho, H., et al. (2014). A secreted peptide acts on BIN2-mediated Greenham,K.,Santner,A.,Castillejo,C.,Mooney,S.,Sairanen,I.,
phosphorylationofARFstopotentiateauxinresponseduringlateral Ljung, K., and Estelle, M. (2011). The AFB4 auxin receptor is
rootdevelopment.Nat.CellBiol.16:66–76. anegativeregulatorofauxinsignalinginseedlings.Curr.Biol.21:
Cobb, A.H., and Reade, J.P.H. (2010). Herbicides and Plant Physi- 520–525.
ology.(Hoboken,NJ:Wiley-Blackwell). Guilfoyle,T.J.(2015).ThePB1domaininauxinresponsefactorand
Cong,L.,Ran, F.A.,Cox, D., Lin, S.,Barretto, R., Habib, N., Hsu, Aux/IAAproteins:aversatileproteininteractionmoduleintheauxin
P.D., Wu, X., Jiang, W., Marraffini, L.A., and Zhang, F. (2013). response.PlantCell27:33–43.
MultiplexgenomeengineeringusingCRISPR/Cassystems.Science Guilfoyle,T.J.,andHagen,G.(2007).Auxinresponsefactors.Curr.
339:819–823. Opin.PlantBiol.10:453–460.
Darwin, C., and Darwin, F.E. (1880). The Power of Movement in Guilfoyle,T.J.,andHagen,G.(2012).GettingagraspondomainIII/IV
Plants.(NewYork:DAppletonandCo.). responsible for Auxin Response Factor-IAA protein interactions.
DelloIoio,R.,Nakamura,K.,Moubayidin,L.,Perilli,S.,Taniguchi, PlantSci.190:82–88.
M., Morita, M.T., Aoyama, T., Costantino, P., and Sabatini, S. Haagen-Smit, A.J., Dandliker, W.B., Wittwer, S.H., and Murneek,
(2008).Ageneticframeworkforthecontrolofcelldivisionanddif- A.E. (1946). Isolation of 3-indoleacetic acid from immature corn
ferentiationintherootmeristem.Science322:1380–1384. kernels.Am.J.Bot.33:118–120.
SCFTIR1/AFB-BasedAuxinPerception 17
Hagen,G.,andGuilfoyle,T.(2002).Auxin-responsivegeneexpres- Lau, S., Shao, N., Bock, R., Jürgens, G., and De Smet, I. (2009).
sion:genes,promotersandregulatoryfactors.PlantMol.Biol.49: Auxinsignalinginalgallineages:factormyth?TrendsPlantSci.14:
373–385. 182–188.
Hamann,T., Mayer, U., and Jürgens, G. (1999). The auxin-insensitive Lavy,M.,Prigge,M.J.,Tigyi,K.,andEstelle,M.(2012).Thecyclo-
bodenlosmutationaffectsprimaryrootformationandapical-basal philin DIAGEOTROPICA has a conserved role in auxin signaling.
patterning in the Arabidopsis embryo. Development 126: 1387– Development139:1115–1124.
1395. Lee, S., Sundaram, S., Armitage, L., Evans, J.P., Hawkes, T.,
Hardtke, C.S., and Berleth, T. (1998). The Arabidopsis gene MO- Kepinski, S., Ferro, N., and Napier, R.M. (2014). Defining bind-
NOPTEROSencodesatranscriptionfactormediatingembryoaxis ingefficiencyandspecificityofauxinsforSCF(TIR1/AFB)-Aux/IAA
formationandvasculardevelopment.EMBOJ.17:1405–1411. co-receptorcomplexformation.ACSChem.Biol.9:673–682.
Havens, K.A., Guseman, J.M., Jang, S.S., Pierre-Jerome, E., Li, J., et al. (2005). Arabidopsis H+-PPase AVP1 regulates auxin-
Bolten, N., Klavins, E., and Nemhauser, J.L. (2012). A synthetic mediatedorgandevelopment.Science310:121–125.
approach reveals extensive tunability of auxin signaling. Plant Li,J.F.,Norville,J.E.,Aach,J.,McCormack,M.,Zhang,D.,Bush,
Physiol.160:135–142. J.,Church,G.M.,andSheen,J.(2013).Multiplexandhomologous
Hellmann,H.,Hobbie,L.,Chapman,A.,Dharmasiri,S.,Dharmasiri, recombination-mediated genome editing in Arabidopsis and Nicotiana
N.,delPozo,C.,Reinhardt,D.,andEstelle,M.(2003).Arabidopsis benthamianausingguideRNAandCas9.Nat.Biotechnol.31:688–691.
AXR6encodesCUL1implicatingSCFE3ligasesinauxinregulation Liscum, E., and Reed, J.W. (2002). Genetics of Aux/IAA and ARF
ofembryogenesis.EMBOJ.22:3314–3325. actioninplantgrowthanddevelopment.PlantMol.Biol.49:387–400.
Hertel,R.,Thomson,K.-S.,andRusso,V.E.A.(1972).In-vitroauxin Long, J.A., Ohno, C., Smith, Z.R., and Meyerowitz, E.M.(2006).
binding to particulate cell fractions from corn coleoptiles. Planta TOPLESSregulatesapicalembryonicfateinArabidopsis.Science
107:325–340. 312:1520–1523.
Holland,A.J.,Fachinetti,D.,Han,J.S.,andCleveland,D.W.(2012). Lozano-Juste,J.,andCutler,S.R.(2014).Plantgenomeengineering
Inducible,reversiblesystemfortherapidandcompletedegradation infullbloom.TrendsPlantSci.19:284–287.
of proteins in mammalian cells. Proc. Natl. Acad. Sci. USA 109: Luerssen,H.,Kirik,V.,Herrmann,P.,andMiséra,S.(1998).FUS-
E3350–E3357. CA3encodesaproteinwithaconservedVP1/AB13-likeB3domain
Hori,K.,etal.(2014).Klebsormidiumflaccidumgenomerevealspri- whichisoffunctionalimportancefortheregulationofseedmatu-
maryfactorsforplantterrestrialadaptation.Nat.Commun.5:3978. rationinArabidopsisthaliana.PlantJ.15: 755–764.
Hyun,Y.,Kim,J.,Cho,S.W.,Choi,Y.,Kim,J.S.,andCoupland,G. Mähönen,A.P.,tenTusscher,K.,Siligato,R.,Smetana,O.,Díaz-
(2015).Site-directedmutagenesisinArabidopsisthalianausingdi- Triviño,S.,Salojärvi,J.,Wachsman,G.,Prasad,K.,Heidstra,R.,
vidingtissue-targetedRGENoftheCRISPR/Cassystemtogener- andScheres,B.(2014).PLETHORAgradientformationmechanism
ateheritablenullalleles.Planta241:271–284. separatesauxinresponses.Nature515:125–129.
Jiang,W.,Yang,B.,andWeeks,D.P.(2014).EfficientCRISPR/Cas9- Mali, P., Yang, L., Esvelt, K.M., Aach, J., Guell, M., DiCarlo, J.E.,
mediated gene editing in Arabidopsis thaliana and inheritance of Norville, J.E., and Church, G.M. (2013). RNA-guided human ge-
modifiedgenesintheT2andT3generations.PLoSONE9:e99225. nomeengineeringviaCas9.Science339:823–826.
Jones,A.M.,Im,K.H.,Savka,M.A.,Wu,M.J.,DeWitt,N.G.,Shillito, Mauseth, J.D. (1991). Botany: An Introduction to Plant Biology.
R.,andBinns,A.N.(1998).Auxin-dependentcellexpansionmedi- (Philadelphia:Saunders).
atedbyoverexpressedauxin-bindingprotein1.Science282:1114– Mockaitis, K., and Estelle, M. (2008). Auxin receptors and plant
1117. development:anewsignalingparadigm.Annu.Rev.CellDev.Biol.
Jönsson, H., Heisler, M.G., Shapiro, B.E., Meyerowitz, E.M., and 24:55–80.
Mjolsness,E.(2006).Anauxin-drivenpolarizedtransportmodelfor Moon, J., Zhao, Y., Dai, X., Zhang, W., Gray, W.M., Huq, E., and
phyllotaxis.Proc.Natl.Acad.Sci.USA103:1633–1638. Estelle,M.(2007).AnewCULLIN1mutanthasalteredresponses
Jurado,S.,Abraham,Z.,Manzano,C.,López-Torrejón,G.,Pacios, tohormonesandlightinArabidopsis.PlantPhysiol.143:684–696.
L.F.,andDelPozo,J.C.(2010).TheArabidopsiscellcycleF-box Nagpal, P., Walker, L.M., Young, J.C., Sonawala, A., Timpte, C.,
proteinSKP2Abindstoauxin.PlantCell22:3891–3904. Estelle,M.,andReed,J.W.(2000).AXR2encodesamemberofthe
Jürgens,G.(1995).Axisformationinplantembryogenesis:cuesand Aux/IAAproteinfamily.PlantPhysiol.123:563–574.
clues.Cell81:467–470. Nanao, M.H., et al. (2014). Structural basis for oligomerization of
Kanke, M., Kodama, Y., Takahashi, T.S., Nakagawa, T., and auxintranscriptionalregulators.Nat.Commun.5:3617.
Masukata,H.(2012).Mcm10playsanessentialroleinoriginDNA Nishimura, K., Fukagawa, T., Takisawa, H., Kakimoto, T., and
unwinding after loading of the CMG components. EMBO J. 31: Kanemaki,M.(2009).Anauxin-baseddegronsystemfortherapid
2182–2194. depletionofproteinsinnonplantcells.Nat.Methods6:917–922.
Katsir,L.,Chung,H.S.,Koo,A.J.K.,andHowe,G.A.(2008).Jasm- Nishimura,K.,andKanemaki,M.(2014).Rapiddepletionofbudding
onatesignaling:aconservedmechanismofhormonesensing.Curr. yeast proteins via the fusion of an auxin-inducible degron (AID).
Opin.PlantBiol.11:428–435. Curr.Protoc.CellBiol.64:20.9.1–20.9.16.
Kazan, K., and Manners, J.M. (2009). Linking development to de- Okushima,Y.,etal.(2005).FunctionalgenomicanalysisoftheAUXIN
fense: auxin in plant-pathogen interactions. Trends Plant Sci. 14: RESPONSEFACTORgenefamilymembersinArabidopsisthaliana:
373–382. uniqueandoverlappingfunctionsofARF7andARF19.PlantCell17:
Kepinski, S., and Leyser, O. (2005). The Arabidopsis F-box protein 444–463.
TIR1isanauxinreceptor.Nature435:446–451. Ouellet,F.,Overvoorde,P.J.,andTheologis,A.(2001).IAA17/AXR3:
Korasick,D.A.,Westfall,C.S.,Lee,S.G.,Nanao,M.H.,Dumas,R., biochemicalinsightintoanauxinmutantphenotype.PlantCell13:
Hagen, G., Guilfoyle, T.J., Jez, J.M., and Strader, L.C. (2014). 829–841.
MolecularbasisforAUXINRESPONSEFACTORproteininteraction Overvoorde, P.J., et al. (2005). Functional genomic analysis of the
andthecontrolofauxinresponserepression.Proc.Natl.Acad.Sci. AUXIN/INDOLE-3-ACETIC ACID gene family members in Arabi-
USA111:5427–5432. dopsisthaliana.PlantCell17:3282–3300.
18 ThePlantCell
Paponov, I.A., Teale, W., Lang, D., Paponov, M., Reski, R., and Scheres, B. (1999). An auxin-dependent distal organizer of
Rensing, S.A., and Palme, K. (2009). The evolution of nuclear patternandpolarityintheArabidopsisroot.Cell99:463–472.
auxinsignalling.BMCEvol.Biol.9:126. Samejima,K.,Ogawa,H.,Ageichik,A.V.,Peterson,K.L.,Kaufmann,S.
Paque,S.,Mouille,G.,Grandont,L.,Alabadí,D.,Gaertner,C.,Goyallon, H.,Kanemaki,M.T.,andEarnshaw,W.C.(2014).Auxin-inducedrapid
A.,Muller,P.,Primard-Brisset,C.,Sormani,R.,Blázquez,M.A.,and degradation of Inhibitor of Caspase Activated DNase (ICAD) induces
Perrot-Rechenmann,C.(2014).AUXINBINDINGPROTEIN1linkscell apoptoticDNAfragmentation,caspaseactivationandcelldeath.J.Biol.
wallremodeling,auxinsignaling,andcellexpansioninArabidopsis.Plant Chem.289:31617–31623.
Cell26:280–295. Salisbury,F.B.,andRoss,C.W.(1992).PlantPhysiology.(Belmont,
Parry,G.,Calderon-Villalobos,L.I.,Prigge,M.,Peret,B.,Dharmasiri, CA:Wadsworth).
S., Itoh, H., Lechner, E., Gray, W.M., Bennett, M., and Estelle, M. Sato, A., and Yamamoto, K.T. (2008). Overexpression of the non-
(2009).ComplexregulationoftheTIR1/AFBfamilyofauxinreceptors. canonicalAux/IAAgenescausesauxin-relatedaberrantphenotypes
Proc.Natl.Acad.Sci.USA106:22540–22545. inArabidopsis.Physiol.Plant.133:397–405.
Pérez, A.C., and Goossens, A. (2013). Jasmonate signalling: Sauer, M., Balla, J., Luschnig, C., Wisniewska, J., Reinöhl, V.,
acopycatofauxinsignalling?PlantCellEnviron.36:2071–2084. Friml, J., and Benková, E. (2006). Canalization of auxin flow by
Petersson, S.V., Johansson, A.I., Kowalczyk, M., Makoveychuk, Aux/IAA-ARF-dependentfeedbackregulationofPINpolarity.Genes
A.,Wang,J.Y.,Moritz,T.,Grebe,M.,Benfey,P.N.,Sandberg,G., Dev.20:2902–2911.
andLjung,K.(2009).AnauxingradientandmaximumintheAra- Schiml, S., Fauser, F., and Puchta, H. (2014). The CRISPR/Cas
bidopsisrootapexshownbyhigh-resolutioncell-specificanalysis systemcanbeusedasnucleaseforinplantagenetargetingandas
ofIAAdistributionandsynthesis.PlantCell21:1659–1668. pairednickasesfordirectedmutagenesisinArabidopsisresultingin
Pierre-Jerome,E.,Jang,S.S.,Havens,K.A.,Nemhauser,J.L.,and heritableprogeny.PlantJ.80:1139–1150.
Klavins,E.(2014).Recapitulationoftheforwardnuclearauxinre- Sheard,L.B.,etal.(2010).Jasmonateperceptionbyinositol-phosphate-
sponse pathway in yeast. Proc. Natl. Acad. Sci. USA 111: 9407– potentiatedCOI1-JAZco-receptor.Nature468:400–405.
9412. Shimizu-Mitao,Y.,andKakimoto,T.(2014).Auxinsensitivitiesofall
Ploense,S.E.,Wu,M.F.,Nagpal,P.,andReed,J.W.(2009).Again- Arabidopsis Aux/IAAs for degradation in the presence of every
of-function mutation inIAA18 alters Arabidopsis embryonic apical TIR1/AFB.PlantCellPhysiol.55:1450–1459.
patterning.Development136:1509–1517. Shin, R., Burch, A.Y., Huppert, K.A., Tiwari, S.B., Murphy, A.S.,
Prigge, M.J., Lavy, M., Ashton, N.W., and Estelle, M.(2010). Guilfoyle, T.J., and Schachtman, D.P. (2007). The Arabidopsis
Physcomitrella patens auxin-resistant mutants affect conserved transcription factor MYB77 modulates auxin signal transduction.
elementsofanauxin-signalingpathway.Curr.Biol.20:1907–1912. PlantCell19:2440–2453.
Rademacher,E.H.,Lokerse,A.S.,Schlereth,A.,Llavata-Peris,C.I., Shinohara,N.,Taylor,C.,andLeyser,O.(2013).Strigolactonecan
Bayer,M.,Kientz,M.,FreireRios,A.,Borst,J.W.,Lukowitz,W., promoteorinhibitshootbranchingbytriggeringrapiddepletionof
Jürgens,G.,andWeijers,D.(2012).Differentauxinresponsemachineries theauxineffluxproteinPIN1fromtheplasmamembrane.PLoSBiol.
controldistinctcellfatesintheearlyplantembryo.Dev.Cell17:211–222. 11:e1001474.
Ramos, J.A., Zenser, N., Leyser, O., and Callis, J. (2001). Rapid Skaar,J.R.,Pagan,J.K.,andPagano,M. (2013).Mechanismsand
degradationofauxin/indoleaceticacidproteinsrequiresconserved functionofsubstraterecruitmentbyF-boxproteins.Nat.Rev.Mol.
aminoacidsofdomainIIandisproteasomedependent.PlantCell CellBiol.14:369–381.
13:2349–2360. Sorefan,K.,Girin,T.,Liljegren,S.J.,Ljung,K.,Robles,P.,Galván-
Raven, P.H., Evert, R.F., and Eichhorn, S.E. (1992). Biology of Ampudia, C.S., Offringa, R., Friml, J., Yanofsky, M.F., and
Plants,5thed.(NewYork:WorthPublishers). Østergaard, L. (2009). A regulated auxin minimum is required for
Reed,J.W.(2001).RolesandactivitiesofAux/IAAproteinsinArabi- seeddispersalinArabidopsis.Nature459:583–586.
dopsis.TrendsPlantSci.6:420–425. Sterling,T.M.,andHall,J.C.(1997).Mechanismofactionofnatural
Reinhardt, D., Mandel, T., and Kuhlemeier, C. (2000). Auxin regu- auxinsandtheauxinicherbicides.InHerbicideActivity:Toxicology,
latestheinitiationandradialpositionofplantlateralorgans.Plant Biochemistry, and Molecular Biology, R.M. Roe, J.D. Burton, and
Cell12:507–518. R.J.Kuhr,eds(Amsterdam:IOSPress),pp.111–141.
Reinhardt,D.,Pesce,E.-R.,Stieger,P.,Mandel,T.,Baltensperger, Su,L.,Bassa,C.,Audran,C.,Mila,I.,Cheniclet,C.,Chevalier,C.,
K., Bennett, M., Traas, J., Friml, J., and Kuhlemeier, C.(2003). Bouzayen, M., Roustan, J.P., and Chervin, C. (2014). The auxin
Regulationofphyllotaxisbypolarauxintransport.Nature426:255– Sl-IAA17 transcriptional repressor controls fruit size via the regu-
260. lation of endoreduplication-related cellexpansion. PlantCell Physiol.
Remington,D.L.,Vision,T.J.,Guilfoyle,T.J.,andReed,J.W.(2004). 55:1969–1976.
ContrastingmodesofdiversificationintheAux/IAAandARFgene Szemenyei, H., Hannon, M., and Long, J.A. (2008). TOPLESS me-
families.PlantPhysiol.135:1738–1752. diates auxin-dependent transcriptional repression during Arabi-
Rogg, L.E., Lasswell, J., and Bartel, B. (2001). A gain-of-function dopsisembryogenesis.Science319:1384–1386.
mutationinIAA28suppresseslateralrootdevelopment.PlantCell Tan,X.,Calderon-Villalobos,L.I.,Sharon,M.,Zheng,C.,Robinson,
13:465–480. C.V.,Estelle,M.,andZheng,N.(2007).Mechanismofauxinper-
Rouse, D., Mackay, P., Stirnberg, P., Estelle, M., and Leyser, O. ceptionbytheTIR1ubiquitinligase.Nature446:640–645.
(1998). Changes in auxin response from mutations in an AUX/IAA Tatematsu, K., Kumagai, S., Muto, H., Sato, A., Watahiki, M.K.,
gene.Science279:1371–1373. Harper, R.M., Liscum, E., and Yamamoto, K.T. (2004). MASSU-
Ruegger, M., Dewey, E., Gray, W.M., Hobbie, L., Turner, J., and GU2encodesAux/IAA19,anauxin-regulatedproteinthatfunctions
Estelle, M. (1998). The TIR1 protein of Arabidopsis functions in together with the transcriptional activator NPH4/ARF7 to regulate
auxin response and is related to human SKP2 and yeast grr1p. differentialgrowthresponsesofhypocotylandformationoflateral
GenesDev.12:198–207. rootsinArabidopsisthaliana.PlantCell16:379–393.
Sabatini, S., Beis, D., Wolkenfelt, H., Murfett, J., Guilfoyle, T., Thimman, K.V. (1977). Hormone Action in the Whole Life of Plants.
Malamy,J., Benfey,P.,Leyser,O.,Bechtold, N., Weisbeek,P., (Amherst,MA:UniversityofMassachusettsPress).