Cell cell interactions.ppt
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The document discusses the composition and functions of the extracellular matrix (ECM) and cell-cell junctions. The ECM provides structural support to cells and regulates cell behavior. It is composed of fibrous proteins like collagen, polysaccharides like glycosaminoglycans, and adhesion proteins like fibronectin and laminin. Cells interact with the ECM through integrin receptors. Cell-cell junctions allow communication between cells and include adherens junctions, desmosomes, tight junctions, and gap junctions. The ECM and cell-cell junctions are essential for tissue structure and function.
Cell cell interactions.ppt
- 2. Readings and Objectives • Reading – Cooper: Chapter 14 • Topics • The Extracellular Matrix • Composition • Cell-Matrix Interactions • Cell-Cell Interactions 2
- 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. 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. 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. • 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. • 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. • 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. • 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. • 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. • 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. • 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. 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. 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. 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. 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. 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. 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. 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. Cell to Cell Junctions Four types of Cell-Cell connections in animal cells • Adherens Junctions • Desmosomes • Tight Junctions • Gap Junctions 20
- 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. 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. Tight Junctions • Tight junctions provide minimal adhesive strength between the cells, usually associated with adherens junctions and desmosomes in a junctional complex 23
- 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. 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. 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. 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. 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