The Molecular Biology of Cadherins

458 Pages·2013·19.131 MB·English

by  Frans van Roy (Eds.)

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CONTRIBUTORS
PanosZ.Anastasiadis
DepartmentofCancerBiology,MayoClinic,Jacksonville,Florida,USA
GeertBerx
DepartmentforMolecularBiomedicalResearch,UnitofMolecularandCellularOncology,
VIB&DepartmentofBiomedicalMolecularBiology,GhentUniversity,Ghent,Belgium
Fa´timaCarneiro
FacultyofMedicine,UniversityofPorto;CancerGeneticsGroup,InstituteofMolecular
PathologyandImmunologyoftheUniversityofPorto(IPATIMUP),andDepartmentof
Pathology,CentroHospitalardeSa˜oJoa˜o,Porto,Portugal
ClaudioCollinet
InstitutdeBiologieduDe´veloppementdeMarseilleLuminy(IBDML),UniteMixtede
Recherche6216,Case907,Marseille,France
ElisabettaDejana
IFOM,FIRCInstituteofMolecularOncology,andDepartmentofBiosciences,Schoolof
Sciences,UniversityofMilan,Milan,Italy
DanielJ.Dickinson1
CancerBiologyProgram,StanfordUniversity,Stanford,California,USA
AzizEl-Amraoui
InstitutPasteur,Unite´deGe´ne´tiqueetPhysiologiedel’Audition;InsermUMRS1120,and
UPMC,Paris,France
JoanaFigueiredo
CancerGeneticsGroup,InstituteofMolecularPathologyandImmunologyoftheUniversity
ofPorto(IPATIMUP),Porto,Portugal
AlexanderGheldof
DepartmentforMolecularBiomedicalResearch,UnitofMolecularandCellularOncology,
VIB&DepartmentofBiomedicalMolecularBiology,GhentUniversity,Ghent,Belgium
Andre´ M.Goffinet
DevelopmentalNeurobiology,UniversityofLouvain,InstituteofNeuroscience,Box
B1.73.16,Brussels,Belgium
KathleenJ.Green
DepartmentofPathology;DepartmentofDermatology,andTheRobertH.Lurie
ComprehensiveCancerCenter,NorthwesternUniversityFeinbergSchoolofMedicine,
Chicago,Illinois,USA
1Presentaddress:DepartmentofBiology,UniversityofNorthCarolina,ChapelHill,NorthCarolina,
USA
xi
xii Contributors
IsmailSahinGul
DepartmentforMolecularBiomedicalResearch,VIB&DepartmentofBiomedical
MolecularBiology,GhentUniversity,Ghent,Belgium
JeffHardin
DepartmentofZoology,andPrograminCellularandMolecularBiology,Universityof
Wisconsin,Madison,Wisconsin,USA
TeruyoshiHirayama
KOKOROBiologyGroupandJST-CREST,LaboratoriesforIntegratedBiology,Graduate
SchoolofFrontierBiosciences,OsakaUniversity,Yamadaoka,Suita,Osaka,Japan
JiYeonHong
TheCatholicUniversityofKorea,CatholicHighPerformanceCellTherapyCenter,505
Banpo-dong,Seocho-gu,Seoul,SouthKorea
PacoHulpiau
DepartmentforMolecularBiomedicalResearch,VIB&DepartmentofBiomedical
MolecularBiology,GhentUniversity,Ghent,Belgium
IreneKahr
DepartmentforMolecularBiomedicalResearch,VIB&DepartmentofBiomedical
MolecularBiology,GhentUniversity,Ghent,Belgium
AntonisKourtidis
DepartmentofCancerBiology,MayoClinic,Jacksonville,Florida,USA
AndrewP.Kowalczyk
DepartmentofCellBiology;DepartmentofDermatology,andTheWinshipCancer
Institute,EmoryUniversitySchoolofMedicine,Atlanta,Georgia,USA
ThomasLecuit
InstitutdeBiologieduDe´veloppementdeMarseilleLuminy(IBDML),UniteMixtede
Recherche6216,Case907,Marseille,France
TimothyLoveless
PrograminCellularandMolecularBiology,UniversityofWisconsin,Madison,Wisconsin,
USA
AllisonLynch
DepartmentofZoology,UniversityofWisconsin,Madison,Wisconsin,USA
KenjiMandai
DivisionofMolecularandCellularBiology,KobeUniversityGraduateSchoolofMedicine,
andCREST,JapanScienceandTechnologyAgency,Kobe,Hyogo,Japan
PierreD.McCrea
DepartmentofBiochemistryandMolecularBiology,TheUniversityofTexasMDAnderson
CancerCenter,andPrograminGenesandDevelopment,TheUniversityofTexasGraduate
SchoolofBiomedicalSciences,Houston,Texas,USA
HelenMcNeill
SamuelLunenfeldResearchInstitute,andDepartmentofMolecularGenetics,Universityof
Toronto,Toronto,Canada
Contributors xiii
RachelK.Miller
DepartmentofBiochemistryandMolecularBiology,TheUniversityofTexasMDAnderson
CancerCenter,Houston,Texas,USA
WilliamA.Mun˜oz
DepartmentofBiochemistryandMolecularBiology,TheUniversityofTexasMDAnderson
CancerCenter,andPrograminGenesandDevelopment,TheUniversityofTexasGraduate
SchoolofBiomedicalSciences,Houston,Texas,USA
W.JamesNelson
DepartmentofBiology;DepartmentofMolecularandCellularPhysiology,andCancer
BiologyProgram,StanfordUniversity,Stanford,California,USA
SiuP.Ngok
DepartmentofCancerBiology,MayoClinic,Jacksonville,Florida,USA
CarlaOliveira
ExpressionRegulationinCancerGroup,InstituteofMolecularPathologyandImmunology
oftheUniversityofPorto(IPATIMUP),andFacultyofMedicine,UniversityofPorto,
Porto,Portugal
ChristinePetit
InstitutPasteur,Unite´ deGe´ne´tiqueetPhysiologiedel’Audition;InsermUMRS1120;
UPMC,andColle`gedeFrance,Paris,France
JonathanPettitt
DepartmentofMolecularandCellBiology,UniversityofAberdeenInstituteofMedical
Sciences,Aberdeen,UnitedKingdom
HugoPinheiro
ExpressionRegulationinCancerGroup,InstituteofMolecularPathologyandImmunology
oftheUniversityofPorto(IPATIMUP),Porto,Portugal
RashmiPriya
DivisionofMolecularCellBiology,InstituteforMolecularBioscience,TheUniversityof
Queensland,St.Lucia,Brisbane,Australia
GlennL.Radice
DepartmentofMedicine,CenterforTranslationalMedicine,JeffersonMedicalCollege,
Philadelphia,Pennsylvania,USA
AparnaRatheesh
DivisionofMolecularCellBiology,InstituteforMolecularBioscience,TheUniversityof
Queensland,St.Lucia,Brisbane,Australia
YoshiyukiRikitake
DivisionofMolecularandCellularBiology,DivisionofCardiovascularMedicine,and
DivisionofSignalTransduction,KobeUniversityGraduateSchoolofMedicine,Kobe,
Hyogo,Japan
AndrewT.Schiffmacher
DepartmentofAnimalandAvianSciences,UniversityofMaryland,1405AnimalSciences
Center,CollegePark,Maryland,USA
xiv Contributors
RaquelSeruca
FacultyofMedicine,UniversityofPorto,andCancerGeneticsGroup,InstituteofMolecular
PathologyandImmunologyoftheUniversityofPorto(IPATIMUP),Porto,Portugal
PraveerSharma
SamuelLunenfeldResearchInstitute,andDepartmentofMolecularGenetics,Universityof
Toronto,Toronto,Canada
YoheiShimono
DivisionofMolecularandCellularBiology,KobeUniversityGraduateSchoolofMedicine,
Kobe,Hyogo,Japan
YoshimiTakai
DivisionofMolecularandCellularBiology,KobeUniversityGraduateSchoolofMedicine,
andCREST,JapanScienceandTechnologyAgency,Kobe,Hyogo,Japan
LisaA.Taneyhill
DepartmentofAnimalandAvianSciences,UniversityofMaryland,1405AnimalSciences
Center,CollegePark,Maryland,USA
FadelTissir
DevelopmentalNeurobiology,UniversityofLouvain,InstituteofNeuroscience,Box
B1.73.16,Brussels,Belgium
FransvanRoy
DepartmentforMolecularBiomedicalResearch,VIB&DepartmentofBiomedical
MolecularBiology,GhentUniversity,Ghent,Belgium
KarlVandepoele1
DepartmentforMolecularBiomedicalResearch,VIB&DepartmentofBiomedical
MolecularBiology,GhentUniversity,Ghent,Belgium
DietmarVestweber
Max-Planck-InstituteofMolecularBiomedicine,Muenster,Germany
WilliamI.Weis
DepartmentofMolecularandCellularPhysiology;CancerBiologyProgram,and
DepartmentofStructuralBiology,StanfordUniversity,Stanford,California,USA
TakeshiYagi
KOKOROBiologyGroupandJST-CREST,LaboratoriesforIntegratedBiology,Graduate
SchoolofFrontierBiosciences,OsakaUniversity,Yamadaoka,Suita,Osaka,Japan
AlphaS.Yap
DivisionofMolecularCellBiology,InstituteforMolecularBioscience,TheUniversityof
Queensland,St.Lucia,Brisbane,Australia
1Currentaddress:LaboratoryforClinicalBiology,GhentUniversityHospital,Ghent,Belgium
PREFACE
ItiswithpleasureandgreatsatisfactionthatIhavebeeneditingthisvolumeon
the Molecular Biology of Cadherins. The cadherin research field is fairly
young.In1987,theTakeichigroupwasthefirsttocloneacadherincDNA
andtodemonstratethecell–celladhesionpropertiesoftheencodedprotein
(Nagafuchietal.,Nature1987;329:341–3).Now,some25yearslater,thefield
hasgrowntofullmaturity.Thecadherinsuperfamilyconsistsofmorethan
100 members in mammals. The roles of these cadherins and cadherin-like
molecules are many. They involve the development and homeostasis of
numerous tissue types in all multicellular metazoans. The hallmark of
cadherins is the presence of a single extracellular domain composed largely
ofcalcium-binding“cadherinrepeats,”whicharetypicallyinvolvedinspe-
cificintercellularrecognitionandjunctionformation.Thisbasicstructurehas
remained fairly constant over millions of years, whereas the cytoplasmic
domains of several cadherin family members have evolved to different
extents.Thishasallowedthedifferentcadherinstointeractwithawiderange
ofcytoplasmicproteins.Theseinteractionscontributetostructuralandreg-
ulatoryassociationswithplasmamembranecomponents,cytoskeletalstruc-
tures,andvariousintracellularsignalingpathways.Whilecadherinssuffered
forlongfromtheconnotation“molecularglue,”itturnedoutthatthis“glue”
is highly sophisticated, not only allowing cells in tissues to recognize each
other and to form coherent functional structures but also to drive cellular
behavior,selectivedifferentiation,regenerativeremodeling,andmanymore
processes.Soitisnotsurprisingthatdefectsincadherinsuperfamilymembers
areresponsibleforawidevarietyofhumanpathologies.Cadherinsandtheir
manyinteractionpartnerscouldthereforeserveastherapeutictargets.
Thisvolumeprovidesthereaderwithacomprehensiveandtimelyover-
viewofthenumerousstructuresandfunctionsofmanyrepresentativemem-
bers of the large cadherin superfamily and of the proteins interacting with
thesecadherins.Severalofthecadherintypesarepresentedforthefirsttime
nexttoeachotherinasinglevolume,andallthecontributionsarebyexpert
researchers in the field. In part, this volume serves as a solid basis for trans-
lationalsciencetoappreciateandexploittheuniquepropertiesofcadherins
and their interaction partners.
Thefirstsectionofthisvolume(A)isonthemolecularbiologyofclassic
cadherinsandtheirassociatedproteinsknownascatenins.Thefounderofthe
xv
xvi Preface
cadherinsuperfamilyandalsoitsbeststudiedrepresentativeistheepithelial
E-cadherin. The assembly of cadherin-dependent cell–cell junctions is dis-
cussedindetailaswellastheirroleintheestablishmentofepithelialcellpolarity.
Novelinsightsintothefieldhaveemphasizedtheroleofcadherininteractions
withcontractilecytoskeletalactomyosinnetworksinmediatingbothstability
andplasticityofthejunctions.Further,cadherin-drivensignalinginfluencesthe
delicatebalancesofRhoGTPasefamilymembers.Inparticular,a-cateninand
armadillocateninsarekeyplayersintheseregulatorynetworks,asexemplified
notonlybyintriguingresultsobtainedfromstudyingthearchaicslimemold
Dictyosteliumdiscoideumbutalsobyadiverserangeoforiginalapproachesinvitro
andinvivoinbothinvertebrateandvertebratesystems.
Thenextsection(B)dealswiththeversatilityofthecadherinandcatenin
superfamilies,whichisapproachedbycomprehensivephylogeneticanalyses.
Thedatasummarizedhereemphasizethepresenceofprototypicmembersin
organismsasbasicasplacozoansandseaanemones,andalsotheremarkable
diversificationofthesuperfamilyinmorerecentlyevolvedmetazoans.This
relates to functional specializations as exemplified by the roles of desmo-
somalcadherinsandVE-cadherin.Desmosomalcadherinsdifferfromclassic
cadherinsinmanyrespectsandplayindispensabletighteningrolesintissues
underphysicaltension,suchastheepidermisandcardiacmuscle,asisclearin
severaldiseaseconditions.Ontheotherhand,VE-cadherin(cadherin-5)is
important for the formation and regulation of endothelial cell junctions,
whichaffectsvasculogenesis,angiogenesis,andvascularpermeabilityunder
various conditions.
Protocadherinsmakeupalargepartofthecadherinsuperfamilyandexist
in two flavors, the more ancient ones, encoded by discrete genes, and the
more modern ones, encoded by clustered genes. Although the biology of
protocadherins is still largely enigmatic, recent studies indicate important
rolesintheestablishmentofthecountlessandcomplexneuronalinteractions
in vertebrates, in regulatory cross-talk with classic cadherins, and in an
increasing number of human pathologies. Other atypical cadherin families
include the Celsr proteins (flamingo in Drosophila), which show intriguing
featuresintermsofplanarcellpolarity(PCP)phenotypes,forinstance,dur-
ing mouse brain development. Further, Fat and Dachsous cadherins stand
out by their extended ectodomains and by their exclusive signaling roles
in PCP and growth control pathways. They have been studied mainly in
Drosophila, but data on vertebrates are emerging.
The following section (C) focuses on specific cadherin functions and
cadherintypeswitchesduringtheembryonicdevelopmentofrepresentative
Preface xvii
model organisms and compares that knowledge to the effect of cadherin
abnormalitiesinhumandiseasemodelsandinpatients.Thenematodeworm
Caenorhabditis elegans is an elegant and powerful model for elucidating the
developmental roles of both cadherins and their cytoplasmic interaction
partners. More recently, genome-wide functional screens have further
extended theusefulness ofthis animalmodel inorder toidentify and study
novel interaction partners of cadherin–catenin complexes. Genetic engi-
neering of mice has likewise turned out to be invaluable for elucidating
the developmental and morphogenetic roles of cadherins, as demonstrated
byextensivestudiesofN-cadherinintheheartandotherorgans.Inviewof
their close homology, it is remarkable that N-cadherin and E-cadherin
behave so differently in both normal and cancerous conditions. Complex
and consecutive switches in cadherin type expression are frequent and rel-
evant during neural crest cell generation, migration, and terminal differen-
tiation. Both the underlying signaling and the resulting morphogenetic
processes are rich topics for further research. Epithelial-to-mesenchymal
transition (EMT) occurs both in normal development and during progres-
sion of tumor cells to higher malignancy. It turned out that an intricate
network of transcriptional repressors is involved in the induction of
EMT-causinggenesignatures.Anotherwaybywhichhumancancersaffect
E-cadherin functionality is germline mutation, which has been shown to
drivefamilialcancerswithdiffusetumorcelldistributions,suchashereditary
diffusegastriccancerandinheritedlobularbreastcancer.Cadherindefectsin
human pathologies are not restricted to cancerous conditions, as defects in
morethan20cadherintypeshavebeenlinkedtoinheritedhumandiseases,
includingskinandhairdisorders,cardiomyopathies,deafness,blindness,and
psychiatric disorders.
Inthelastsection(D),fullattentionisgiventoaselectionofcytoplasmic
interaction partners of classic cadherins. These proteins have turned out to
be also often involved in key signaling processes at both cytoplasmic and
nuclearlocations.Forexample,b-cateninisfamousforitsroleinthecanon-
icalWntsignalingpathway.Lesswellunderstoodaretherolesofthevarious
members of the p120 armadillo protein subfamily, including p120-catenin
itself and several homologs, as well as plakophilins. Besides their important
influencesonjunctionalstabilityandonactivationofRhofamilyGTPases,
evidence is growing for a crosstalk between these proteins and nuclear
b-cateninactivity.Thefinalcontributionisdevotedtoafadin/AF6,acyto-
plasmicproteininteractingwithnumerousproteinsatornearbytheplasma
membrane. This important protein plays pleiotropic functions, including
xviii Preface
regulation of the formation of cadherin-mediated cell junctions and of
several other cellular processes and their key signaling cascades.
Insummary,thisvolumecoverstheexcitingfieldofthemolecularbiology
ofcadherinsinawideandcomprehensiveway,includingbioinformaticana-
lyses,advancedinvitroassays,geneticsofsmallmodelorganisms,generationof
relevantmousemodels,anddiscussionofmanyrelevantandimportanthuman
diseases.Iamgratefultothemanyauthorswhomadeexpertandvaluablecon-
tributions to this reference work, which will be of much interest to many
researchers in various disciplines. Finally, I am particularly grateful to Amin
Bredan,Ph.D.,whocontributedsignificantlytothisvolumebymeticulously
editing and optimizing the originally submitted manuscripts.
FRANS VAN ROY
Ghent University and VIB
CHAPTER ONE
Roles of Cadherins and Catenins in
(cid:1)
Cell Cell Adhesion and Epithelial
Cell Polarity
W. James Nelson*,†,‡, Daniel J. Dickinson‡,1, William I. Weis†,‡,}
*
DepartmentofBiology,StanfordUniversity,Stanford,California,USA
†DepartmentofMolecularandCellularPhysiology,StanfordUniversity,Stanford,California,USA
‡CancerBiologyProgram,StanfordUniversity,Stanford,California,USA
}DepartmentofStructuralBiology,StanfordUniversity,Stanford,California,USA
1Presentaddress:DepartmentofBiology,UniversityofNorthCarolina,ChapelHill,NorthCarolina,USA
Contents
1. Introduction:TheBasicDesignofPolarizedEpithelialCells 4
2. Cadherin-MediatedCell–CellAdhesionandtheFunctionofPolarityProteins
inApical–BasalCellPolarity 7
3. OtherFunctionsofE-Cadherin,Catenins,and“PolarityProtein”Complexes
inMaintainingEpithelialHomeostasis 11
4. Cadherin,Catenins,andtheOriginsofEpithelialPolarity 13
Acknowledgments 18
References 18
Abstract
Asimpleepitheliumisthebuildingblockofallmetazoansandamulticellularstageof
a nonmetazoan. It comprises a closed monolayer of quiescent cells that surround a
luminalspace.Cellsareheldtogetherbycell–celladhesioncomplexesandsurrounded
byextracellularmatrix.Theseextracellularcontactsarerequiredfortheformationofa
polarized organization of plasma membrane proteins that regulate the directional
absorptionandsecretionofions,proteins,andothersolutes.Whileadvanceshavebeen
made in understanding how proteins are sorted to different plasma membrane
domains, less is known about how cell–cell adhesion is regulated and linked to the
developmentofepithelialcellpolarityandregulationofhomeostasis.
ProgressinMolecularBiologyandTranslationalScience,Volume116 #2013ElsevierInc. 3
ISSN1877-1173 Allrightsreserved.
http://dx.doi.org/10.1016/B978-0-12-394311-8.00001-7