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Cell cell interactions.ppt

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Cell cell interactions.ppt

  1. 1. Extracellular Matrix
  2. 2. Readings and Objectives • Reading – Cooper: Chapter 14 • Topics • The Extracellular Matrix • Composition • Cell-Matrix Interactions • Cell-Cell Interactions 2
  3. 3. Extracellular Matrix Introduction • Cell walls: bacteria, fungi, algae, and higher plants • Animal cell in tissues embedded in an extracellular matrix of proteins and polysaccharides Function • Provides structural support to cells and tissues • Important role in regulating cell behavior –Cell to cell interaction, communication 3
  4. 4. General Structure of Extracellular Matrix • Animal cells embedded in an extracellular matrix • Basal laminae: thin layer on which epithelial cells rest. Also surrounds muscle cells, adipose cells, and peripheral nerves • most abundant in connective tissues • Connective tissue – loose connective tissue – Bone – tendon – cartilage 4
  5. 5. Composition of Extracellular Matrix • Fibrous proteins • Polysaccharides- gel like environment • Adhesion proteins- link components of the matrix to one another and to cells • Different matrices have different amounts of each component – Tendons, rich in fibrous proteins – Cartilage, high in polysaccharides – Bone, calcium phosphate crystal deposition 5
  6. 6. • Collagen- major structural fibrous protein • Forms triple helices • Triple helix domains: repeats of the amino acid sequence Gly-X-Y • Glycine in every 3rd position • X=Pro, packs helices closely • Y= hydroxyproline, synthesized in ER • Pro, Hpro stabilizes by helping H-bonding Matrix composition: Collagen 6
  7. 7. • Type I collagen- the most abundant • polypeptide chains have about 330 Gly-X-Y repeats • Secreted through ER/golgi, form collagen fibrils • Triple helical molecules are associated in regular staggered arrays • Covalent cross-links: lysine and hydroxylysine side chains • strengthen the fibrils • Fibrils form collagen fibers, several µm in diameter Matrix composition: Collagen 7
  8. 8. • Some are not fibril forming • Fibril-associated collagens: bind to collagen fibrils, link to others or to other matrix components • Network-forming collagens: have non helical interruption, cross-link to network • Anchoring fibrils: link basal laminae to underlying connective tissues • Transmembrane collagens: proteins that participate in cell- matrix interactions Types of Collagen 8 Network-forming collagens
  9. 9. • Extracellular matrix gels are polysaccharides called glycosaminoglycans (GAGs). • GAGs are repeating units of disaccharides: One sugar is either N-acetylglucosamine or N-acetylgalactosamine, the second is usually acidic (glucuronic acid or iduronic acid). Matrix Polysaccharides 9
  10. 10. • sulfate groups make GAGs negatively charged • bind positively charged ions and trap water molecules to form hydrated gel • GAGs are linked to proteins to form proteoglycans Matrix Polysaccharides 10
  11. 11. • Link matrix components – to each other – to cell surfaces • Fibronectin : main adhesion protein of connective tissues • A homodimeric protein (2500 aa/subunit), binds – collagen and GAGs – cells • Recognized by cell surface receptors • Attachment of cells to the extracellular matrix Matrix Adhesion proteins: Fibronectin 11
  12. 12. • Laminin: adehsion protein of basal laminae • Heterotrimeric: α, β, and γ-chains (5, 4, 3 genes, respectively) • have binding sites for – cell surface receptors, eg integrins – type IV collagen – Proteoglycans • Assemble to cross-linked network • Linking cells and matrix Matrix Adhesion proteins: Laminins 12
  13. 13. Cell-Matrix Interactions • Integrins: major cell surface receptors, involved in attachment of cells to the extracellular matrix • Transmembrane proteins, heterodimer of α and β subunits (18α, 8β) • Bind to short aa in, – Collagen – Fibronectin – laminin • also anchor the cytoskeleton to the extracellular matrix 13
  14. 14. Cell-Matrix Junctions Two types of cell-matrix junction • Focal adhesions: bundles of actin filaments are anchored to β subunits of integrins via – α-actinin – Vinculin via talin • Assembly of focal adhesions • Focal complex: small group of integrins • Recruite Talin, Vinculin, α- actinin and Formin • Formin initiates actin bundles 14
  15. 15. Focal adhesions are reversible • Integrins can reversibly bind matrix components • change conformation between active and inactive states • Inactive state: integrin heads turned close to cell surface • Cell signaling extends heads to matrix • Migrating cells: focal adhesions form at the leading edge 15
  16. 16. Cell-Matrix Junctions: Hemidesmosomes • Hemidesmosomes anchor epithelial cells to the basal lamina • α6β4 integrins bind to lamins • long cytoplasmic tail of β subunit binds to intermediate filaments via • Plectin and BP230 and BP180 (similar to transmembrane collagens) 16
  17. 17. Cell-Cell interactions • Interactions between cells are critical for development and function of multicellular organisms • Cell-cell interactions: – Transient: activation of immune cells; migration to injury site – Stable: role in the organization of tissues. • Cell-Cell junctions allow rapid communication between cells • During embryo development, cells from one tissue specifically adhere to cells of the same tissue rather than cells of a different tissue 17
  18. 18. Cell-Cell interactions • Cell-cell adhesion- mediated by four groups of cell adhesion molecules • Selectins, integrins, the immunoglobulin (Ig) superfamily, and cadherins • Many adhesions are divalent cation-dependent, requiring Ca2+, Mg2+ or Mn2+ 18
  19. 19. Selectins • Selectins- transient interactions between leukocytes and endothelial cells • Leukocytes slow down, flattened, migrate from the circulation to sites of tissue inflammation • initial adhesion • stable adhesions binding of integrins to intercellular adhesion molecules (ICAMs) on endothelial cells 19
  20. 20. Cell to Cell Junctions Four types of Cell-Cell connections in animal cells • Adherens Junctions • Desmosomes • Tight Junctions • Gap Junctions 20
  21. 21. Adherens Junctions • Cadherin form stable cell-cell connections involve actin filaments • Also include β-catenin, p120, and α-catenin, • β-catenin and p120 bind to cadherin and help maintain stability • β-catenin binds α-catenin that interacts with actin filament of cytoskeleton 21
  22. 22. Desmosomes • link the intermediate filament of adjacent cells • Desmoglein and desmocollin (transmembrane cadherins) bind by heterophilic interactions across the junction • Plakoglobin and plakophilin bind to the cadherins and link to the intermediate filament binding protein, desmoplakin 22
  23. 23. Tight Junctions • Tight junctions provide minimal adhesive strength between the cells, usually associated with adherens junctions and desmosomes in a junctional complex 23
  24. 24. Tight Junctions • Tight junctions in epithelial cell form a seal that prevents free passage of molecules and ions between cells • separate apical and basolateral domains of the plasma membrane • prevent free diffusion of lipids and membrane proteins 24
  25. 25. Tight Junctions • transmembrane proteins, occludin, claudin, and junctional adhesion molecule (JAM), anchored on F-actin • Bind similar proteins on the adjacent cell • Sealing the space between cells 25
  26. 26. Gap Junctions • open channels through the plasma membrane • allowing ions and small molecules to diffuse freely • Proteins and nucleic acids can not pass through • heart muscle cells, passage of ions through gap junctions synchronizes the contractions of neighboring cells • allow passage of some signaling molecules, such as cAMP and Ca2+, coordinating responses of cells in tissues 26
  27. 27. Gap Junctions • Gap junctions are made of transmembrane proteins in the connexin family • 6 connexins form a cylinder with an open aqueous pore in its center, called a connexon • Connexons in the plasma membrane adjacent cells align • form open channels between the two cytoplasms 27
  28. 28. Gap Junctions • Specialized gap junctions occur on specific nerve cells and form an electrical synapse • Individual connexons can be opened or closed • When open, they allow rapid passage of ions between the two nerve cells 28

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