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1、Cell Junction, Adhesion and Extracellular MatrixHow cells are organized in multicellular organisms?A cross-sectional view of part of the wall of the intestine. This long, tubelike organ is constructed from epithelial tissue (red), connective tissue (green), and muscle tissue (yellow). Each tissue is
2、 an organized assembly of cells held together by cell-cell Molecular Biology of the Cell. 4th editionOutline1.Cell Junction2.Cell Adhesion3.The Extracellular MatrixCell Junction is the direct interactions of cells with their neighbouring cells or extracellular matrix at particular site of contact.Ce
3、ll Adhesion is the binding of a cell to a surface, an extracellular matrix or another cell.The Extracellular Matrix (ECM) is the non-cellular component present within all tissues and organs. GlossaryCell Junction (细胞连接细胞连接)Occluding junction (封闭连接封闭连接): Tight junctions (紧密连接紧密连接)Anchoring junction (
4、锚定连接锚定连接): Adhesion belt (黏着带黏着带), Adhesion plaque (黏着斑黏着斑)，Desmosome (细胞桥粒细胞桥粒), Hemidesmosome (半桥粒半桥粒)Communicating junction (通讯连接通讯连接): Gap junctions (间隙连接), Chemical SynapsesCell Adhesion (细胞黏附细胞黏附)Cadherin (钙黏素钙黏素)Integrin (整合素整合素)Selectin (选择素选择素)The immunoglobulin superfamily (IgSF) cell adhe
5、sion molecules (IgSF CAM, 免疫球免疫球蛋白超家族细胞黏附分子蛋白超家族细胞黏附分子)Extracellular Matrix (胞外基质胞外基质)Collagen (胶原胶原)Glycosaminoglycans (GAG, 糖胺聚糖糖胺聚糖)Proteoglycan (PG, 蛋白聚糖蛋白聚糖)Elastin (弹性蛋白弹性蛋白)Fibronectin (FN, 纤黏连蛋白纤黏连蛋白)Laminin (LN, 层黏连蛋白层黏连蛋白)Cell Junction:Occluding junction (Tight junction)Anchoring junction
6、(Adherent junction)Communicating junction (Gap junction)Example 1. Epithelial Cell JunctionsCell JunctionExample 2. Endothelial Cell JunctionsCell Junctions Found in the CellCell JunctionsOccluding junctionTight JunctionsTight Junction MoleculesOccludin, ClaudinTight Junction Functions: Transcellula
7、r & Paracellular TransportAnchoring junctionActin filaments: Adhesion beltAdhesion plaqueIntermediate filaments:DesmosomeHemidesmosomeAdhesion beltVelcroCAMs Mediate Cell-cell Adhesion & Link to CytoskeletonAdhesion plaqueFocal AdhesionIntegrin (Red)Actin filamentsActin (Green)DesmosomeThe molecular
8、 composition of desmosomesHemidesmosomeAnchoring junctionIntracellular SkeletonTransmembrane Cell adhesive molecules(CAM)IntegrinCadherinHemidesmosomeDesmosomeIntermediate filamentsAdhesion plaqueAdhesion beltActin filamentsCell/ECMCell/CellPlasmodesmataPlasmodesmata are narrow channels that act as
9、intercellular cytoplasmic bridges to facilitate communication and transport of materials between plant cells. Communicating Junctions:Plasmodesmata-Plant cellsGap junctionsChemical SynapsesGap JunctionsGap junction molecular composition 1.5nmGap Junctions ControlCardiomyocyte Gap Junctions is essent
10、ial for synchronous heart contraction Chemical SynapsesThe molecular composition of neuronal junctionsA Historical ViewDiscovering the Molecular Components of Intercellular Junctions.Cold Spring Harb Perspect Biol. 2009;1:a003061 Further readingQuestion: What is the roles of hepatocytes junctions in
11、 bile production?Hepatic lobuleCell Adhesion（细胞黏附）（细胞黏附）Cell adhesion is the binding of a cell to a surface or substrate, such as an extracellular matrix of another cell. Leukocyte Adhesion on Vascular WallCell Adhesion Moleclues (CAMs)Cadherin StructureExtracellular domains of a classical cadherin
12、(C-cadherin)CadherinCalcium-dependence of cadherins-mediated cell adhesionCell CultureClassical cadherins : E-cadherin, epitheliaN-cadherin, neuronP-cadherin, placentaVE-cadherin, endotheliaNon classical cadherin: Demoglein, desmosomeDesmocollin, desmosomeCadherin functions：Cadherins allow cells to
13、sort themselvesCompaction of an early mouse embryo.At the 8-cell stage they start expressing E-cadherinsEpithelial-Mesenchymal Transition (EMT)EMT and metastasisIntegrin-transmembrane receptors that are the bridges for cell-cell and cell-extracellular matrix (ECM) interactionsAdhesion plaqueIntegrin
14、 mediates both cell anchoring and adhesionLeukocyte adhesionThe superfamily of integrinstransmembrane receptors that are the bridges for cell-cell and cell-extracellular matrix (ECM) interactionsThe Structure of IntegrinsThe Features of Integrin ligands Dynamics of Integrins ActivationIntegrin IIb3
15、mediates dual-directions signals regulate platelet activation.AggregationSpreadingClots RetractionHemostasisIntegrin IIb3 mutation-Glanzmanns ThrombastheniaClinical Manifestations: Mucocutaneous bleeding at birth or early infancy (gum bleeding, epistaxis)Drug target-Integrin IIb3 for Acute Coronary
16、SyndromesThrombosisAbciximabIntegrilinBarry S. CollerFibrinogenSelectinsComposed of a lectin domain, an EGF-like region3 selectins have been describedL-selectin: Found in all leukocytes, binds to activated endothelial cells (ECs)E-selectin: Found on activated ECs, binds to neutrophils, monocytes and
17、 some T cellsP-selectin: Found on Platelets, ECs and binds to neutrophils, monocytes and some T cells Immunoglobulin superfamily Cell adhesion molecules，IgSF CAMs (Ca2+-independent adhesion)The Extracellular Matrix Organic fibrilar matrix Organic nonfibrilar matrix WaterCell originFibroblastsSmooth
18、muscle cellsChondroblastsOsteoblasts and epitelial cellsExtracellular Matrix (ECM)Fibrous protein: Collagen ElastinFibronectinLamininGlycosaminoglycan (GAG) and proteoglycans Components of ECMBasal lamina Provides support anchorage Regulates cells dynamic behavior:- polarity of cells- cell different
19、iation- adhesion- migration Provides mechanical support for tissues and organ architecture- growth- regenerative and healing processes - determination and maintenance of the structure Place for active exchange of different metabolites, ions, waterFunctions of ECMCollagen structureGlycine, proline, h
20、ydroxyprolineTriple helix (three fibers interwined together)Collagen subtypes, anchors, receptors and distributionAnchorProteoglycan ReceptorCells Tissue IChS, DSfibrobl.Skin, tendon,bone, ligaments, dentinIIFibrinectin ChSIntegrinchondrocyteCartilage, vitreus humorIIIHS, HephepatocyteSkin, muscle,
21、blood vesselsepithelIV LamininHS, Heplaminin rec. epithelAll basal laminaesendothelhepatocyteVFibrinectin HS, HepIntegrinresting fibrobl. Similar to type I, fetal tissueVI Fibrinectin HSIntegrinresting fibrobl.VIILamininFibronectinIntegrinSkinGenetic disorders of collagenCollagen IOsteogenesis imper
22、fectaEhlers-Danlos syndrome type VIICollagen IIMultiple diseases of cartilageCollagen IIIEhlers-Danlos syndrome type IVCollagen IVAlport syndrome, stroke, hemorrhage, porencephalyCollagen VIIDystrophic epidermolysis bullosa (skin blistering)Ehlers-Danlos Syndrome-Cutis HyperelasticaDystrophic epider
23、molysis bullosa-Mutations in the COL7A1 gene6.5 per million newborns in the United StatesLaminin (consisting of three polypeptides a a, b b, g g)They are a major component of the basal lamina, a protein network foundation for most cells and organs. Stretching of a network of elastin moleculesElastin
24、 is highly hydrophobicMainly two features: hydrophobic and cross-linked segmentsHydrophobic segments provide elasticityCross-linking provides stability ElastinFibronectin (crucial for angiogenesis)Glycosaminoglycan (GAG) and proteoglycans The extracellular matrix dynamic and cell functionsMetallopro
25、teinases (MMPs)Cells that need to migrate must first break down the connections to the ECM (e.g. tissue repair, metastasis of tumors) MMPs can be:-secreted in active form (collagenase)-secreted as inactive form (e.g. plasminogen is inactive until it is modified by “plasminogen activators)-activated when cells stop secreting TIMPs (tissue inhibitors of metalloproteinases) Christian Frantz, Kathleen M. Stewart and Valerie M. Weaver.The extracellular matrix at a glance.J Cell Sci. 2010; 123, 4195-4200. Further ReadingSummary
