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Cytoskelet Plus Matrix Deel2
 

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 Cytoskelet Plus Matrix Deel2 Presentation Transcript

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