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Cytoskelet Plus Matrix Deel2
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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
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    • 1.  
    • 2. Desmosomes: Cell-cell junctions linked to intermediate filaments
    • 3. Desmosomes: Cell-cell junctions linked to intermediate filaments
    • 4. Focal adhesions: cell-matrix connections linked to actin filaments Actin Vinculin Major component: Integrins
    • 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  
    • 6. Hemidesmosomes: cell-matrix connections linked to intermediate filaments Major component: Integrins, (but different from integrins in focal adhesions)
    • 7. Gap junctions: Pores between cells Made of connexins Function: Regulated transport small molecules Coordination.
    • 8.  
    • 9. Integrins are regulated: Inside-out signalling
    • 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
    • 11. Cell migration: making and breaking of cell matrix junctions
    • 12. Figure 16-87 Molecular Biology of the Cell (© Garland Science 2008)
    • 13. GFP paxilin: a focal adhesion protein
    • 14. Focal Adhesions: Dynamic structure that mediates migration
    • 15. Adhesion and cell migration: Important events in differentiation
    • 16. Adhesion and cell migration: Important events in inflammation
    • 17. Adhesion and cell migration: Important events in metastasering
    • 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.
    • 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)
    • 20. Different kinesins and dyneins for different functions kinesin dynein
    • 21. Complex of proteins determines specificity of cargo
    • 22. ATP binding: Sweep forward; hydrolysis: no binding, ADP release: binding
    • 23. ATP binding: no binding; hydrolysis: sweep forward; P release: binding ADP release: Power stroke
    • 24. Many different myosines for different functions
    • 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
    • 26.  

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