Table Of ContentHandbook of
Experimental Pharmacology
Volume 165
Editor-in-Chief
K. Starke, Freiburg i.Br.
Editorial Board
G.V.R. Born, London
M. Eichelbaum, Stuttgart
D. Ganten, Berlin
F. Hofmann, M(cid:2)nchen
B. Kobilka, Stanford, CA
W. Rosenthal, Berlin
G. Rubanyi, Richmond, CA
D
Berlin
Heidelberg
NewYork
HongKong
London
Milan
Paris
Tokyo
Cell Adhesion
Contributors
G. Berx, L. Borradori, T. Brabletz, P.F. Bradfield, H.-J. Choi,
S. Getsios, L.M. Godsel, K.J. Green, A.K. Horst, A.C. Huen,
W. Ikeda, B.A. Imhof, K. Irie, R.L. Juliano, J. Koster,
Y. Miyamoto, U. M(cid:2)ller, W.J. Nelson, B. Nieswandt,
S. Offermanns, T.D. Perez, P. Reddig, T. Sakisaka, H. Semb,
K. Shimizu, A. Sonnenberg, E.T. Stoeckli, K. Strumane,
Y. Takai, F. Van Roy, C. Wagener, W.I. Weis
Editors
J(cid:2)rgen Behrens and W. James Nelson
B D
Professor
Dr.J(cid:2)rgenBehrens
Nikolaus-Fiebiger-Zentrum
f(cid:2)rMolekulareMedizin
Universit(cid:3)tErlangen-N(cid:2)rnberg
Gl(cid:2)ckstrasse6
91054Erlangen,Germany
e-mail:[email protected]
W.JamesNelson,Ph.D.
DepartmentofMolecular&CellularPhysiology
BeckmanCenterB121
StanfordUniversitySchoolofMedicine
Stanford,CA94305-5345
USA
e-mail:[email protected]
With59Figuresand10Tables
ISSN0171-2004
ISBN3-540-20941-7Springer-VerlagBerlinHeidelbergNewYork
LibraryofCongressCataloging-in-PublicationData
Celladhesion/contributors,GBerx...[etal.];editors,J(cid:2)rgenBehrens andW.JamesNelson.
p.m.–(Handbookofexperimentalpharmacology;v.165)
Includesbibliographicalreferencesandindex.
ISBN3-540-20941-7(alk.paper)
1. Celladhesionmolecules. 2. Celladhesion.I.Berx, G. II.Behrens,J(cid:2)rgen,Dr.III. Nelson,W. J.
(W.James)IV.Series.
QP905.H3vol.165 [QP552.C42] 615'.1s–dc22 [571.6] 2004042951
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Preface
Aswithotherareasofbiologicalresearch,theprogressthathasbeenmadeover
thepast25yearsinthefieldofcelladhesionisimpressive.Inthelate1970s,the
searchforspecificcellsurfacereceptorsforadhesionprocesseswasinitiatedus-
ing mainly biochemical and immunological approaches. Since then, the intro-
duction of novel methods of cellular and molecular biology and powerful tech-
niquesformanipulatinggeneexpressionintransgenicandknock-outmicehave
greatly advanced the field. Not only do we now know the precise molecular
structureofmanyofthe cell adhesionreceptorsthatwerepostulatedto exist in
the early days, but we have a clear picture of their function, and evidence of
theirinvolvementinsignaltransduction.Wehavealsofoundcluestotheroleof
cell adhesion in normal embryonal development and adult physiology, and we
haveevidencethatdisturbanceincelladhesioncancausedisease.
Inthisvolume,ourgoalwastoprovideanoverviewofthemaintopicsofcur-
rent cell adhesionresearch, includingstructural analyses ofcell adhesionmole-
cules and studies of their functionalrole invitroand invivo. Wehave focussed
mainly onthe four major families of cell-adhesion receptors, i.e. the cadherins,
the integrins, the Ig superfamily and the selectin-based adhesion system. The
chapters by Perez and Nelson and Choi and Weis describe the structural basis
of cadherin function, focussing on the extracellular domain of cadherins and
thecytoplasmictailinteractionswithcatenins,respectively.Sembreviewsthein
vivo functions of cadherins with an emphasis on normal embryonal develop-
ment, and Strumaneet al. describethe alterationsofcadherins in cancerdevel-
opment and metastasis. A chapter by Brabletz is devoted to the in vivo role of
the catenins, highlighting the signal transduction function of b-catenin in the
Wnt pathway. The molecular composition and function of desmosomes are the
topicofthechapterbyGodselandcolleagues,introducingdesmosomalcadherins
and their link to the cytoskeleton. Integrins are dealt with in three reviews: an
overview ofsignaltransductiontriggeredby integrin-mediated adhesion is giv-
en by Miyamoto et al., the in vivo function of integrins as revealed by mouse
models is described by M(cid:2)ller, and the role of integrins and associated compo-
nents in the hemidesmosome is reviewed by Koster and co-authors. In the sec-
tiononIgsuperfamilyadhesionreceptors,HorstandWagenerandIrieandcol-
leagues describe the structure and cellular function of two major subfamilies,
VI Preface
the CEACAMs and nectins, respectively. Stoeckli has contributed a chapter on
theroleoftheIgsuperfamily inbrain developmentwherethe diversityofthese
adhesionreceptorsisparticularly prominent.Two chaptersdealwiththephysi-
ological function of adhesion receptors in the adult organism. The chapter by
BradfieldandImhoffocussesonleukocyte–endotheliuminteractionsandintro-
duces the selectins and their interplay with Ig receptors and integrins, and the
chapter byNieswandt and Offermanns deals withplatelet aggregationin hemo-
stasis and thrombosis, where detailed molecular analysis has already reached
thelevelofpharmacologicalapplication.
Whatwillbethefuturetrendsincelladhesionresearchandthepotentialap-
plicationof this knowledge for human disease, and inparticular for pharmaco-
logical applications (which is the underlying interest of this handbook series)?
It can be expected that our knowledge of the in vivo functions of cell adhesion
receptors and mechanisms will continueto increase as more mouse models are
generated. Naturally, this will have an impact on our understanding of disease
processesthatarerelatedtodefectivecelladhesion.Paradigmsforthis,toname
only two, are the implications of E-cadherin being a metastasis suppressor in
human cancer, or the detailed knowledge ofblood clotting being based on spe-
cific cell adhesion processes. Moreover, the perception of cell adhesion mole-
cules as signalling receptorsandtheirdetailed structuralanalysiswill hopefully
set the stage for new pharmacological approaches. Thus, cell adhesion research
willstayasexcitingasithasbeen.
I hope that this book will serve as a helpful guide for students and for re-
searchers from other disciplines, and also be a valuable source of reference for
ourcolleaguesinthefield.
J(cid:2)rgenBehrens,Erlangen
List of Contributors
(Addressesstatedatthebeginningofrespectivechapters)
Berx,G. 69 Nelson,W.J. 3
Borradori,L. 243 Nieswandt,B. 437
Brabletz,T. 105
Bradfield,P.F. 405 Offermanns,S. 437
Choi,H.-J. 23 Perez,T.D. 3
Getsios,S. 137 Reddig,P. 197
Godsel,L.M. 137
Green,K.J. 137 Sakisaka,T. 343
Semb,H. 53
Horst,A.K. 283 Shimizu,K. 343
Huen,A.C. 137 Sonnenberg,A. 243
Stoeckli,E.T. 373
Ikeda,W. 343 Strumane,K. 69
Imhof,B.A. 405
Irie,K. 343 Takai,Y. 343
Juliano,R.L. 197 VanRoy,F. 69
Koster,J. 243 Wagener,C. 283
Weis,W.I. 23
Miyamoto,Y. 197
M(cid:2)ller,U. 217
List of Contents
PartI.Cadherins
CadherinAdhesion:MechanismsandMolecularInteractions ............ 3
T.D.Perez,W.J.Nelson
StructuralAspectsofAdherensJunctionsandDesmosomes ............. 23
H.-J.Choi,W.I.Weis
CadherinsinDevelopment ........................................ 53
H.Semb
CadherinsinCancer............................................. 69
K.Strumane,G.Berx,F.VanRoy
InVivoFunctionsofCatenins...................................... 105
T.Brabletz
TheMolecularCompositionandFunctionofDesmosomes.............. 137
L.M.Godsel,S.Getsios,A.C.Huen,K.J.Green
PartII.IntegrinsandExtracellularMatrix
RegulationofSignalTransductionbyIntegrins........................ 197
Y.Miyamoto,P.Reddig,R.L.Juliano
IntegrinsandExtracellularMatrixinAnimalModels................... 217
U.M(cid:2)ller
Hemidesmosomes:MolecularOrganizationandTheirImportance
forCellAdhesionandDisease...................................... 243
J.Koster,L.Borradori,A.Sonnenberg
PartIII.ImmunoglobulinSuperfamily
CEA-RelatedCAMs .............................................. 283
A.K.Horst,C.Wagener
X ListofContents
RolesofNectinsinCellAdhesion,SignalingandPolarization............ 343
K.Irie,K.Shimizu,T.Sakisaka,W.Ikeda,Y.Takai
IgSuperfamilyCellAdhesionMoleculesintheBrain ................... 373
E.T.Stoeckli
PartIV.PhysiologyandPathologyofCellAdhesion
AdhesionMechanismsofEndothelialCells ........................... 405
P.F.Bradfield,B.A.Imhof
PharmacologyofPlateletAdhesionandAggregation ................... 437
B.Nieswandt,S.Offermanns
SubjectIndex................................................... 473
