細(xì)胞生物學(xué)2010課件chapter

Chapter15LearningObjectives:1.Extracellularmatrix:ComponentsandFunctions;2.IntegratingCellsintoTissues;3.Cell-Matrixadhension;4.Celljunctons:Cell-celladhensionandcommunication;5.CellWallsExtracellularmatrix,Celljunctionandcelladhension

ExtracellularMatrixandCellWall

Extracellularmatrix(ECM)isnonlivingmaterialaroundcellsinmulticellularorganisms.importanceincell-cellsignaling,woundrepair,celladhesionandtissuefunctionprimarilycomposedofcelluloseinplants,composedofchitininarthropods(節(jié)肢動物）andfungi,carbohydratesandproteinsinvertebrates能夠分泌和形成細(xì)胞外基質(zhì)的主要細(xì)胞類群是成纖維細(xì)胞(fibroblast)和其他特化組織的細(xì)胞。ThreemostobviousformsofECMarebone,cartilageandbasementmembrane.ConnectingCellstotheECMTheECMinteractswiththesurfaceofthecellthroughfibronectin

CellsattachtotheECMbymeansofintegrinsIntegrinsarereceptorproteinswhichareofcrucialimportanceCompositionoftheECM

ProteinsGlycoproteinsCollagensElastinsLamininsFibronectinProteoglycansSeveralsugarsareincorporatedinproteoglycansTheglycosylationoccursintheGolgiapparatusProteoglycansaredegradedinlysosomes膠原(Collagen)◆基本特性：●Collagenisafamilyoffibrousglycoproteinsthatarepresentonlyinextracellularmatrices.●Collagenisthesinglemostabundantproteininthehumanbody(constitutingmorethan25percentofallprotein),●Collagensarefoundthroughouttheanimalkingdomandarenotedfortheirhightensilestrength,thatis,theirresistancetopullingforces.●Collagenisproducedprimarilybyfibroblasts,thecellsfoundinvarioustypesofconnectivetissues,andalsobysmoothmusclecellsandepithelialcells.

◆膠原的類型●Nineteendistincttypesofcollagenhavebeenidentified.●Eachcollagentypeisrestrictedtoparticularlocationswithinthebody,buttwoormoredifferenttypesareoftenpresenttogetherinthesameECM.●Gly-Pro-X(X:多為lys，Pro、lys可糖基化，10％的糖）Structuralfeatures賴氨酸交聯(lián)◆膠原的組裝◆膠原的作用

◆膠原是骨、腱和皮膚組織中的主要蛋白，在這些組織的細(xì)胞外基質(zhì)中,膠原起著細(xì)胞外基質(zhì)骨架作用;

◆膠原具有促進(jìn)細(xì)胞生長的作用;

◆在細(xì)胞分化中，膠原基質(zhì)和提純的膠原底物具有維持并誘導(dǎo)細(xì)胞分化的作用。

膠原酶遺傳缺陷

某些人具有膠原酶的遺傳缺陷，這樣,他們的膠原纖維就不能正確地裝配，其結(jié)果，皮膚和各種其它的結(jié)綈組織就會降低它們的強(qiáng)度變得非常的松弛。皮膚過渡松弛癥核心蛋白多糖

基底膜蛋白多糖

基底膜蛋白多糖聚集蛋白聚糖多糖

蛋白聚糖(Proteoglycan,PG)◆結(jié)構(gòu)與功能

●

Protein-polysaccharidecomplexiscalledaproteoglycan

●Aproteoglycanconsistsofacoreproteinmoleculetowhichchainsofglycosaminoglycans(GAGs,糖胺聚糖)arecovalentlyattached.●BecauseofthenegativechargesborneonthesulfatedGAGs,proteoglycansbindhugenumbersofcations,whichinturnbindlargenumbersofwatermolecules.Asaresult,proteoglycansformaporous,hydratedgelthatfillstheextracellularspacelikepackingmaterialandresistscrushing(compression)forces.

◆透明質(zhì)酸(hyaluronicacid)

是一種糖胺聚糖

細(xì)胞外基質(zhì)中發(fā)現(xiàn)的大多數(shù)糖胺聚糖都是作為蛋白聚糖的一個成分而存在，惟一例外的是透明質(zhì)酸，它在細(xì)胞外

基質(zhì)中也可游離存在。透明質(zhì)酸在結(jié)締組織中起強(qiáng)化、彈性和潤滑作用,具有抗壓能力。彈性蛋白(Elastin)◆是彈性纖維(elasticfibers)的主要成分，主要存在于韌帶和脈管壁?！艄δ埽耗軌蛸x予細(xì)胞外基質(zhì)彈性?！魪椥缘鞍滓彩歉缓拾彼岷透彼岬牡鞍踪|(zhì)。與同膠原不同的是，彈性蛋白的脯氨酸沒有羥基化，所以沒有羥脯氨酸的存在。黏著蛋白

黏著蛋白(adhesiveprotein)是細(xì)胞外基中質(zhì)的第三類成分，之所以將這些蛋白稱為黏著蛋白，主要是這些些蛋白起著將細(xì)胞外基質(zhì)與細(xì)胞聯(lián)系起來的橋梁作用。纖粘連蛋白(Fibronectin,FN)●Fibronectinareafamilyofcloselyrelatedadhesiveglycoproteinsthatwidelydistributedthroughouttheanimalkingdom;●Fibronectinoccursinasolubleforminthebloodandotherbodyfluids；●Asinsolublefibrilsintheextracellularmatrix◆結(jié)構(gòu)特點(diǎn)：■Fibronectinpolypeptideisconstructedfromasequenceofapproximately30independentlyfoldingFndomains■Eachofthetwopolypeptidechainsthatmakeupafibronectinmoleculecontains：●BindingsitesforothercomponentsoftheECM,suchascollagensandproteoglycans.Thesebindingsitesfacilitateinteractionsthatlinkthesediversemoleculesintoastable,interconnectednetwork.●Bindingsitesforreceptorsonthecellsurface，thesebindingsitesholdthecellinastableattachmenttotheECM（eg.RGD(Arg-Gly_Asp).◆功能：◆FN最主要的功能是介導(dǎo)細(xì)胞的黏著?！粲捎贔N具有同時與細(xì)胞外基質(zhì)各類成分相結(jié)合的特點(diǎn),并可促進(jìn)細(xì)胞外基質(zhì)的其它成分的沉積,故認(rèn)為FN是細(xì)胞外基質(zhì)的組織者?！艟S持細(xì)胞形態(tài)；促進(jìn)細(xì)胞遷移；有助于血液凝固和創(chuàng)傷修復(fù)。層粘連蛋白(laminin,LN)◆Lamininsareafamilyofextracellularglycoproteinsthatconsistofthreedifferentpolypeptidechainslinkedbydisulfidebondsandorganizedintoamoleculeresemblingacrosswiththreeshortarmsandonelongarm◆層粘連蛋白主要存在于基膜(basallamina)結(jié)構(gòu)中，是基膜的主要結(jié)構(gòu)成分。Laminin◆層粘連蛋白的功能■首先作為基膜的主要結(jié)構(gòu)成分對基膜的組裝起關(guān)鍵作用。它可作為黏著因子介導(dǎo)細(xì)胞黏著于膠原,使之發(fā)生鋪展?！鯡xtracellularlamininscangreatlyinfluenceacell'spotentialformigration,growth,anddifferentiation.

Matrixmetalloproteinases(MMPs)◆ThedegradationofECMmaterialsisaccomplishedlargelybyafamilyofzinc-containingenzymes?！鬳ithersecretedintotheextra-cellularspaceorboundtotheexternalsurfaceoftheplasmamembrane.◆TheexcessiveorinappropriateactivityofMMPsislikelytocausedisease.Infact,MMPshavebeenimplicatedinanumberofpathologicalconditions,includingarthritis（關(guān)節(jié)炎）（,multiplesclerosis（多發(fā)性硬化）,atherosclerosis（動脈硬化）,toothdecay,andtumorprogression.基膜巢蛋白

基膜的功能：1.對組織起支撐作用2.調(diào)節(jié)分子及細(xì)胞運(yùn)動和滲透性屏障

ConnectingCellstotheECMTheECMinteractswiththesurfaceofthecellthroughfibronectin

CellsattachtotheECMbymeansofintegrinsIntegrinsarereceptorproteinswhichareofcrucialimportance◆細(xì)胞黏著的方式凝集素在細(xì)胞黏著中的作用AdhesionMolecules:

◆Cadherins（鈣粘素）:E-,N-,P-cadherin;dimer/trimercadherinrepeats;Ca2+-dept;Actinfilement;adhesionbelt/chemicalsynapse◆Selectin（選擇素）:L-selectin,P-selectin(withlectin-likedomains);lymphocytehoming,;參與白細(xì)胞與血管內(nèi)皮之間識別與黏著?！鬒g-superfamily,IgSF（免疫球蛋白）:5XIg-likedomains;N-CAM,V-CAM；Ca2+-indept;介導(dǎo)神經(jīng)細(xì)胞間粘著、淋巴細(xì)胞-應(yīng)答細(xì)胞間粘著◆Intergrin（整聯(lián)蛋白）:

Ca2+-dept;α/β亞基形成跨膜dimer;

胞外結(jié)合ECM(FN/LN-RGDsequence);

胞內(nèi)間接結(jié)合Actinfilement。2023/4/1643細(xì)胞粘連分子家族配體識別穩(wěn)定的細(xì)胞連接鈣粘素同嗜性互作粘著連接和橋粒整聯(lián)蛋白胞外基質(zhì)粘著斑和半橋粒免疫球蛋白超家族成員否選擇素碳水化合物否免疫球蛋白整聯(lián)蛋白否超家族同嗜性互作否2023/4/1644細(xì)胞粘著分子主要家族(CAM)

2023/4/1647

緊密連接的存在部位和結(jié)構(gòu)特點(diǎn)◆又叫不通透連接(impermeablejunction),它不僅連接相鄰的細(xì)胞,而且封閉細(xì)胞間隙,使大多數(shù)分子難以在細(xì)胞間通透?！暨@種連接方式普遍存在于腔道上皮細(xì)胞靠近管腔端的相鄰細(xì)胞膜間?！魪慕Y(jié)構(gòu)上看,通過連接蛋白形成焊接線，封閉相鄰細(xì)胞間的空隙。TightJunction(封閉）2023/4/1649Acurrentmodelofatightjunction

緊密蛋白顆粒形成連接線2023/4/1651緊密連接與細(xì)胞極性2023/4/1652AnchoringJunction錨定連接◆又稱斑形成連接(plaque-bearingjunction)◆主要靠黏著蛋白、整聯(lián)蛋白和細(xì)胞骨架體系將相鄰兩細(xì)胞或細(xì)胞與細(xì)胞外基質(zhì)連接在一起?！舭咝纬蛇B接分為：●adhesion黏著連接●desmosome橋粒2023/4/1653

黏著連接

(adherenjunction)

細(xì)胞間的連接作用與細(xì)胞骨架系統(tǒng)的肌動蛋白相關(guān)稱為黏著連接。

●adhesionbelt黏著帶●focaladhesion黏著斑2023/4/1654◆黏著帶(adhesionbelts)●是細(xì)胞-細(xì)胞間黏著的一種方式；●位于上皮細(xì)胞緊密連接的下方；●靠鈣黏著蛋白同肌動蛋白相互作用；●黏著帶處相鄰細(xì)胞質(zhì)膜的間隙為20～25nm,介于緊密連接和橋粒之間。2023/4/1656■參與黏著連接的組分∶●黏著蛋白(cadherin)∶

一種跨膜連接糖蛋，屬Ca2+

依賴的細(xì)胞-細(xì)胞黏著分子，它有三個結(jié)構(gòu)域●細(xì)胞質(zhì)斑(cytoplasmicplaque)∶

含黏著斑蛋白(vinculin)，連環(huán)蛋白（catenin）等，介導(dǎo)肌動蛋白與黏著蛋白相連；●肌動蛋白∶2023/4/1657Adhesionbelts2023/4/1658◆黏著斑

(adhesionplaqua，focaladhesion)

主要特點(diǎn)是：

肌動蛋白纖維通過整聯(lián)蛋白同細(xì)胞外基質(zhì)，如纖粘連蛋白，而不是與另一個細(xì)胞的表面相連。Cell-extracellularjunction2023/4/1659Focaladhesion2023/4/1660橋粒(desmosomes)◆細(xì)胞是通過中間纖維錨定到細(xì)胞骨架上，這種黏著連接方式稱為橋粒?！舴譃椋骸?點(diǎn)狀)橋?！癜霕蛄?。2023/4/1663◆Hemidesmosomes

半橋粒與橋粒連接有兩點(diǎn)差別∶●半橋粒參與連接的跨膜蛋白不是鈣黏著蛋白而是整聯(lián)蛋白；●整聯(lián)蛋白的細(xì)胞外結(jié)構(gòu)域不是與相鄰細(xì)胞的整聯(lián)蛋白相連而是同細(xì)胞外基質(zhì)相連。2023/4/1664Hemidesmosomes2023/4/1665Hemidesmosomes2023/4/1666黏著連接的作用2023/4/1667Asummaryofjunctionalandnonjunctionaladhesivemechanisms.

2023/4/16683CommunicationJunction◆一種特殊的細(xì)胞連接,位于特化的具有細(xì)胞間通訊作用的細(xì)胞