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Lecture 17 - Cell Adhesion

Lecture 17 - Cell Adhesion - Cell-cell interactions and...

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Unformatted text preview: Cell-cell interactions and cell-extracellular matrix interactions: Adhesion Cell junctions provide mechanical strength to support tissues in organisms, and allow cells to directly signal each other in multi-cellular organisms so as to coordinate their behavior and/or their gene expression.They also serve as orientation cues for the assembly of tissues. Cell-cell interactions These interactions must break and reform for cell movement during development and repair Necessary for cancer/ metastasis Extracellular matrix Connective tissues (bone, tendons) are rich in extracellular matrix Epithelial tissues have thin matrix Plants rely exclusively on their extracellular matrix (cell wall) Functional classes of cell junctions in animal cells Stress transmission (cadherins & integrins) Cell cell adhesion Cell matrix adhesion Seal gaps between cells Make channels Local communication tight junctions /passageways between (e.g.synapses & eph-ephrin) (claudins) cells A selective barrier (connexin or innexins) Cells can coordinate and integrate multiple types of cell contacts in junctional complexes Cell junctions in epithelial cells classified by their function Cell junctions connect key cohesive integral membrane proteins to the cytoskeleton via anchor proteins Cadherins mediate homophilic cell-cell adhesions E-cadherins facilitate early cell attachments in the embryo 8-cell Extracellular domains interact homotypically with other cadherins E cadherin expression > compaction Cadherins are responsible for cell sorting into tissues They all share in common the cadherin domain motifs Cadherins are expressed differentially in tissues Cytoplasmic domains interact with a variety of intracellular ligands > 180 in humans Cadherins mediate calcium-dependent cell adhesion Cadherins bind each other weakly, but cooperate like Velcro to attach cells to one another via multiple interactions Apposing cadherins interact head to head and bind calcium at flexible hinges between cadherin repeats Anchoring junctions cluster cadherins and their attached cytoskeletons to form high strength linkages Calcium binding stiffens the cadherin molecules, by preventing bending between repeats Calcium depletion reverses the adhesion process Cytoplasmic catenins link cadherins to the actin cytoskeleton to tie (and coordinate) the actin cytoskeleton of neighboring cells Adherence junctions between epithelial cells of the gut form an adhesion belt by joining actin filament bundles The catenins & other anchors proteins (vinculin, plakoglobin) link actin filaments to cadherins at adherens junctions Release of beta catenin allows it to enter nuclei for signaling… Tightening of the adhesion belt converts cylindrical cells into trapezoids, facilitating the formation of epithelial tubes Desmosomes form connections between cadherins & intermediate filaments to provide mechanical strength Desmosomes form junctions between epidermal cells of mouse skin-appear as buttons or rivets Keratin-based intermediate filaments are attached to desmosomes and hemidesmosomes via anchor proteins Molecular architecture of the desmosome Selectins mediate transient cell-cell interactions in the bloodstream Selectins in endothelial cells bind loosely to carbohydrates in the white blood cell, which roll like tumble weed downstream Subsequent integrin expression in white blood cell allow it to bind ICAM in endothelial cells to create a more stable interaction before entry The Ig-superfamily These are on endothelial cells recognized by integrins in white blood cells not calcium dependent Scaffold proteins organize junctional complexes (e.g. synapse) Two nerve terminals synapsing on a dendrite vesicles synapse Scaffold proteins link various functions under the cell membrane Tight junctions form a seal between cells and a fence between membrane domains Junctional complexes afford coordination and polarity -supported by ZO Tight junctions are generated by claudin molecules arranged in strands Tight junctions are created by rows of homotypic claudin interactions Occludin function ? 24 claudins in humans They form paracellular pores for selective passage of ions such as magnessium in kidneys Tricellulin is required at points where 3 cells meet Gap junctions couple cells electrically and metabolically They form small aqueous pores. Only ions and small metabolites can flow through. Can be regulated. 1.5 nm cutoff Different composition = different permeability All plant cells are linked by plasmodesmata ~ gap junctions The basal lamina underlies all epithelia and surrounds some non-epithelial cells. Has a mechanical support role; a linking role; a barrier role; a filtering role; influences cell polarity, metabolism, promotes survival, proliferation, differentiation, serve as highways for movement of other cells, and as templates for tissue regeneration Skeletal A thin, though, flexible sheet surrounding all epithelia Here lamina serves as support and molecular filter Molecular structure and components of the basal lamina Laminin: a multidomain heterotrimmeric glycoprotein: the organizer, a crosslinking protein Collagen IV a crosslinking protein that provides tensile strength: it is a rope -like superhelix, with segmental bends Perlecan and nidogen serve as linkers between laminin and collagen networks Integrins in the cell plasma membrane link the extracellular matrix to the intracellular actin cytoskeleton fibronectin Hemidesmosomes In most cells, integrins link the actin cytoskeleton to the extracellular matrix using vinculin and talin 24 integrins in humans In epithelia cells (the exception) integrins bridge laminin to keratin intermediate filaments Used in focal adhesion points Integrins are activated by inside-out, and outside-in signaling by crosstalk between signaling pathways Talin competes with integrin alpha for interaction with integrin beta. Separation of alpha-beta integrins leads to activation Extracellular signal Binding of extracellular ligand with RGD peptide Signals received from the outside can change the conformation of talin to activate it to capture ligands Desintegrins are RGD containing anti-clotting proteins in snake venom- make the victim bleed to death Reading covered in this lecture: Alberts et al Chapter 19 pgs 1131-1155; 1158-1172 The inner life of the cell- Biovisions (3 min with music) http://www.youtube.com/watch?v=BVvvx5HGpLg Harvard Cell Animations (8 min narrated version) http://www.youtube.com/watch?v=fZZ3DD_tV9k&feature=related ...
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