Desmosomes are cell-cell junctions linked to intermediate filaments. Focal adhesions are cell-matrix connections linked to actin filaments. Integrins are major components of both focal adhesions and hemidesmosomes, which are also cell-matrix connections but linked to intermediate filaments. Integrins are regulated by changes in avidity through clustering and affinity through activation.

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.

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