CellJunction,AdhesionandExtracellularMatrix

1Howcellsareorganizedinmulticellularorganisms?Across-sectionalviewofpartofthewalloftheintestine.Thislong,tubelikeorganisconstructedfromepithelialtissue(red),connectivetissue(green),andmuscletissue(yellow).Eachtissueisanorganizedassemblyofcellsheldtogetherbycell-cellMolecularBiologyoftheCell.4thedition2OutlineCellJunctionCellAdhesionTheExtracellularMatrixCellJunctionisthedirectinteractionsofcellswiththeirneighbouringcellsorextracellularmatrixatparticularsiteofcontact.CellAdhesionisthebindingofacelltoasurface,anextracellularmatrixoranothercell.TheExtracellularMatrix(ECM)isthenon-cellularcomponentpresentwithinalltissuesandorgans.3GlossaryCellJunction

(細胞連接)Occludingjunction(封閉連接):Tightjunctions

(緊密連接)Anchoringjunction(錨定連接):Adhesionbelt(黏著帶),Adhesionplaque(黏著斑)，Desmosome

(細胞橋粒),Hemidesmosome(半橋粒)Communicatingjunction

(通訊連接):Gapjunctions(間隙連接),ChemicalSynapsesCellAdhesion

(細胞黏附)Cadherin

(鈣黏素)Integrin

(整合素)Selectin

(選擇素)Theimmunoglobulinsuperfamily(IgSF)celladhesionmolecules(IgSFCAM,免疫球蛋白超家族細胞黏附分子)ExtracellularMatrix

(胞外基質(zhì))Collagen

(膠原)Glycosaminoglycans(GAG,糖胺聚糖)Proteoglycan(PG,蛋白聚糖)Elastin(彈性蛋白)Fibronectin(FN,纖黏連蛋白)Laminin(LN,層黏連蛋白)4CellJunction:Occludingjunction(Tightjunction)Anchoringjunction(Adherentjunction)Communicatingjunction(Gapjunction)5Example1.EpithelialCellJunctionsCellJunction6Example2.EndothelialCellJunctions7CellJunctionsFoundintheCellCellJunctions8Occludingjunction9TightJunctions10TightJunctionMoleculesOccludin,Claudin11TightJunctionFunctions:Transcellular&ParacellularTransport12AnchoringjunctionActinfilaments:AdhesionbeltAdhesionplaqueIntermediatefilaments:DesmosomeHemidesmosome13Adhesionbelt14Velcro15CAMsMediateCell-cellAdhesion&LinktoCytoskeleton16AdhesionplaqueFocalAdhesionIntegrin(Red)ActinfilamentsActin(Green)17Desmosome18Themolecularcompositionofdesmosomes19Hemidesmosome20AnchoringjunctionIntracellularSkeletonTransmembraneCelladhesivemolecules(CAM)IntegrinCadherinHemidesmosomeDesmosomeIntermediatefilamentsAdhesionplaqueAdhesionbeltActinfilamentsCell/ECMCell/Cell21PlasmodesmataPlasmodesmataarenarrowchannelsthatactasintercellularcytoplasmicbridgestofacilitatecommunicationandtransportofmaterialsbetweenplantcells.CommunicatingJunctions:Plasmodesmata-PlantcellsGapjunctionsChemicalSynapses22GapJunctions23Gapjunctionmolecularcomposition1.5nm24GapJunctionsControl25CardiomyocyteGapJunctionsisessentialforsynchronousheartcontraction26ChemicalSynapses27Themolecularcompositionofneuronaljunctions28AHistoricalView?DiscoveringtheMolecularComponentsofIntercellularJunctions.ColdSpringHarbPerspectBiol.2009;1:a003061Furtherreading29Question:Whatistherolesofhepatocytes’junctionsinbileproduction?Hepaticlobule30CellAdhesion（細胞黏附）Celladhesionisthebindingofacelltoasurfaceorsubstrate,suchasanextracellularmatrixofanothercell.31LeukocyteAdhesion

on

Vascular

Wall32CellAdhesionMoleclues(CAMs)33CadherinStructureExtracellulardomainsofaclassicalcadherin(C-cadherin)Cadherin34Calcium-dependenceofcadherins-mediatedcelladhesionCellCulture35Classicalcadherins:E-cadherin,epitheliaN-cadherin,neuronP-cadherin,placentaVE-cadherin,endotheliaNonclassicalcadherin:Demoglein,desmosomeDesmocollin,desmosome36Cadherinfunctions：37CadherinsallowcellstosortthemselvesCompactionofanearlymouseembryo.Atthe8-cellstagetheystartexpressingE-cadherins38Epithelial-MesenchymalTransition(EMT)39EMTandmetastasis40Integrin-transmembranereceptorsthatarethebridgesforcell-cellandcell-extracellularmatrix(ECM)interactions41AdhesionplaqueIntegrinmediatesbothcellanchoringandadhesionLeukocyteadhesion42Thesuperfamilyofintegrinstransmembranereceptorsthatarethebridgesforcell-cellandcell-extracellularmatrix(ECM)interactions43The

Structure

of

Integrins44The

Features

of

Integrin

ligands

45DynamicsofIntegrinsActivation46IntegrinαIIbβ3mediatesdual-directionssignalsregulateplateletactivation.AggregationSpreadingClotsRetractionHemostasis47IntegrinαIIbβ3mutation-Glanzmann’sThrombastheniaClinicalManifestations:Mucocutaneousbleedingatbirthorearlyinfancy(gumbleeding,epistaxis)48Drugtarget-IntegrinαIIbβ3forAcuteCoronarySyndromesThrombosisAbciximabIntegrilinBarryS.CollerFibrinogen49SelectinsComposedofalectindomain,anEGF-likeregion3selectinshavebeendescribedL-selectin:Foundinallleukocytes,bindstoactivatedendothelialcells(ECs)E-selectin:FoundonactivatedECs,bindstoneutrophils,monocytesandsomeTcellsP-selectin:FoundonPlatelets,ECsandbindstoneutrophils,monocytesandsomeTcells5051Immunoglobulinsuperfamily

Celladhesionmolecules，IgSF

CAMs(Ca2+-independentadhesion)52TheExtracellularMatrix53

OrganicfibrilarmatrixOrganicnonfibrilarmatrix

WaterCelloriginFibroblastsSmoothmusclecellsChondroblastsOsteoblastsandepitelialcellsExtracellularMatrix(ECM)54Fibrousprotein:CollagenElastinFibronectinLamininGlycosaminoglycan(GAG)andproteoglycansComponentsofECM55Basallamina56ProvidessupportanchorageRegulatescellsdynamicbehavior: -polarityofcells -celldifferentiation -adhesion -migrationProvidesmechanicalsupportfortissuesandorganarchitecture -growth -regenerativeandhealingprocesses -determinationandmaintenanceofthestructurePlaceforactiveexchangeofdifferentmetabolites,ions,waterFunctionsofECM57CollagenstructureGlycine,proline,hydroxyprolineTriplehelix(threefibersinterwinedtogether)58Collagensubtypes,anchors,receptorsanddistributionAnchorProteoglycanReceptorCellsTissueIChS,DSfibrobl.Skin,tendon,bone,ligaments,dentinIIFibrinectinChSIntegrinchondrocyteCartilage,vitreushumorIIIHS,HephepatocyteSkin,muscle,bloodvesselsepithelIVLamininHS,Heplamininrec.epithelAllbasallaminaesendothelhepatocyteVFibrinectinHS,HepIntegrinrestingfibrobl.SimilartotypeI,fetaltissueVIFibrinectinHSIntegrinrestingfibrobl.VIILamininFibronectinIntegrinSkin59GeneticdisordersofcollagenCollagenIOsteogenesisimperfectaEhlers-DanlossyndrometypeVIICollagenIIMultiplediseasesofcartilageCollagenIIIEhlers-DanlossyndrometypeIVCollagenIVAlportsyndrome,stroke,hemorrhage,porencephalyCollagenVIIDystrophicepidermolysisbullosa(skinblistering)Ehlers-DanlosSyndrome-CutisHyperelastica60Dystrophicepidermolysisbullosa-MutationsintheCOL7A1gene6.5permillionnewbornsintheUnitedStates61Laminin

(consistingofthreepolypeptidesa,b,g)Theyareamajorcomponentofthebasallamina,aproteinnetworkfoundationformostcellsandorgans.62StretchingofanetworkofelastinmoleculesElastinishighlyhydrophobicMainlytwofeatures:hydr