Cytoskelet Plus Matrix Deel2

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  • Marc Ginsberg chartered a pathway from Rap to integrins, via Riam and talin two adaptor proteins, but it is alsi easy to postulate a pathway that impinges on the cytoskeleton through the Rac GEFs Vav and Tiam
  • Cytoskelet Plus Matrix Deel2

    1. 2. Desmosomes: Cell-cell junctions linked to intermediate filaments
    2. 3. Desmosomes: Cell-cell junctions linked to intermediate filaments
    3. 4. Focal adhesions: cell-matrix connections linked to actin filaments Actin Vinculin Major component: Integrins
    4. 5. Integrins are regulated by changes in avidity (clustering) and affinity (activation) Adapted: Kinbara, K., Goldfinger, L.E., Hansen, E, Chou, F.-L., Ginsburg, M.H. NRMCB 4 (2003) 767 clustering activation affinity avidity e.g.  M  2 ,  5  1 e.g. ICAM fibronectin  
    5. 6. Hemidesmosomes: cell-matrix connections linked to intermediate filaments Major component: Integrins, (but different from integrins in focal adhesions)
    6. 7. Gap junctions: Pores between cells Made of connexins Function: Regulated transport small molecules Coordination.
    7. 9. Integrins are regulated: Inside-out signalling
    8. 10. Integrins signal back: Outside-in signalling Cells in culture require integrin signalling for cell proliferation and survival Most junction proteins are receptors: outside-in signalling
    9. 11. Cell migration: making and breaking of cell matrix junctions
    10. 12. Figure 16-87 Molecular Biology of the Cell (© Garland Science 2008)
    11. 13. GFP paxilin: a focal adhesion protein
    12. 14. Focal Adhesions: Dynamic structure that mediates migration
    13. 15. Adhesion and cell migration: Important events in differentiation
    14. 16. Adhesion and cell migration: Important events in inflammation
    15. 17. Adhesion and cell migration: Important events in metastasering
    16. 18. Metastasis Early stages of metastases Disruption of adhesion to neighbouring cells. Disruption of adhesion to extracellular matrix. Degradation of surrounding extracellular matrix. Cell migration: Binding to cell matrix 1. 2. 3. 4.
    17. 19. Molecular motors Myosin on Actin: contractility and transport of cargo Kinesin on Tubulin: transport of cargo to plus-end (cell periphery) Dynein on Tubulin: transport of cargo to minus end (cell center)
    18. 20. Different kinesins and dyneins for different functions kinesin dynein
    19. 21. Complex of proteins determines specificity of cargo
    20. 22. ATP binding: Sweep forward; hydrolysis: no binding, ADP release: binding
    21. 23. ATP binding: no binding; hydrolysis: sweep forward; P release: binding ADP release: Power stroke
    22. 24. Many different myosines for different functions
    23. 25. Trafficking and direction of cargo is regulated Pigment granules in fish melanocytes bind to both kinesin and dynein Kinesin: to plus end Dynein: to minus end

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