Cell Junctions and Cell AdhesionCitrawati Dyah Kencono Wungu, dr.

Cells are small, squishy, filled with aqueous mediumWhy can they combine to form a structure as massive, strong, and stable as a horse or tree?It depends on how stresses can be transmitted across a multicellular structureTwo ways:The strength of ECM A complex network of protein & polysaccharide chainsThe strength of cytoskeleton and cell adhesions

Architecture of Animal TissuesConnective tissuesThe ECM is plentiful, and cells are sparsely distributed within itThe main stress-bearing component is ECMEpithelial TissuesThe main sress-bearing component is cytoskeleton linked from cell to cell by anchoring junctionECM is scanty consisting of a thin mat (basal lamina)Cell matrix attachment bond epithelial tissue to the connective tissue beneath it

Two main ways in which animal cells are bound together

Four functional classes of cell junctions in animal tissuesa. Anchoring junction Transmit stresses, tethered to cytoskeletal filaments inside the cellb. Occluding junctions Seal gaps between cells in epithelia Make impermeable/selectively permeable barrierc. Channel-forming junctions Make passageway linking the cytoplasmsd. Signal-relaying junctions Across plasma membranes at contact sites

A summary of the various cell junctions found in a vertebrate epithelial cell, classified according to their primary functions

Cell adhesion consists of two adhesions:Cell-cell adhesionsCell-matrix adhesions

CADHERINSPresent in all multicellular animalsHave high dependence on Ca2+ ions removing Ca2+ from extracellular medium causes adhesions to come adriftThe main adhesion molecules holding cells together in early embryonic tissuesDiversity:Classical cadherin: E-cadherin, N-cadherinRelated in sequenceNon classical cadherin: protocadherin, desmocollin, desmoglein, T-cadherinDistantly related in sequence

Cadherins superfamily

Cadherins mediate homophilic adhesionHomophilic : Cadherin molecules of a specific subtype on one cell bind to cadherin molecules of the same or closely related subtype on adjacent cellThe binding occurs at the N-terminal tips of the cadherin molecules

Cadherin domainsExtracellular domainIntracellular domain

Extracellular DomainCa2+ ions bind to sites near each hinge and prevent flexing rigid rodWhen Ca2+ is removed hinge flex floppyN terminus conformation is changed slightly binding affinity

Cadherins and most other cell adhesion proteins bind with low affinity.Strong attachments result from the formation of many such weak bonds in parallel clustered side to side with many other cadherin molecules on the same cell form a strong anchoring junctionIt can be easily disassembled by separating the molecules sequentially.

Intracellular domainProvide anchorage for filaments of the cytoskeleton:a. Actin : adherens junctions coordinate actin-based motility of adjacent cellsb. Intermediate filaments : desmosome junctions provide mechanical strengthDepends on intracellular anchor proteins on the tail of cadherin main role : -catenin, plakoglobin, p120-catenin (regulation)

Actin-adherens junctions

Desmosome junctionsPlakoglobin : -cateninPlakophilin : 120-p catenin

Three other important cell adhesion proteins SelectinsIntegrinsAdhesive Ig-superfamilies

SelectinsCell-surface carbohydrate binding transmembrane proteins (lectins)Mediate cell-cell adhesion in bloodstreamMain roles: infammatory responses, control the traffic of white blood cells by binding to endothelial cells in blood vesselsL-selectin : white blood cellsP-selectin: platelets & endothelial cellsE-selectin: endothelial cellsCollaborate with integrins

Ig superfamiliesMediate Ca2+ independent cell-cell adhesionHeterophilic binding : ICAMs (Intercellular Cell Adhesion Molecules), VCAMs (Vascular Cell Adhesion Molecules) binding with WBC integrinsHomophilic binding : NCAMs (Neural Cell Adhesion Molecules)

IntegrinsMain role : Cell-matrix adhesionBut also play function on cell-cell adhesion work together with selectins and Ig superfamilies to make WBC go out of the vessel

Integrins24 varieties in humansComposed of 2 noncovalently associated glycoprotein subunits: & Short intracellular C-terminal tails and large N-terminal extracellular domainExtracellular: bind ECM proteinsIntracellular : bind actin filaments viatalin and other intracellular anchorage proteins

Activate intracellular signaling pathways control cells behavior and change in gene expression (depend on cytoplasmic protein tyrosine kinase = focal adhesion kinase)Studies in culture show that many cells will not grow or proliferate unless attached to ECM (anchorage dependence)

Scaffold ProteinsBind to other protein components and assemble them for synapses

Tight JunctionsForm a seal between cells and a fence between membrane domains

Gap junctions and plasmodesmataBridge gaps between adjacent cells create direct passageways from the cytoplasm of one into that of the other exchange small molecules between neighboring cellsAnimals : gap junctionPlants : plasmodesmata

Combined function of cell adhesion

ReferenceAlberts et al. Molecular Biology of The Cell, 5th edition. New York: Garland Science

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