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4.16.2010 lecture 2

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Transcript

  • 1.
    • Integrins
    • 2. EXC Component
    • 3. Globular regions with specific binding site for the RGD sequences on fibronectin or specific binding sites for specific amino acids on laminin
    • 4. Alpha and beta subunit link to alpha helix and the two cytoplasmic domains interact with actin binding proteins that help integrins assemble actin filaments
    • 5. Integrins doent directly link to actin
    • 6. They Indirectly bind to actin by binding to actin binding proteins
    • 7. Intracellular component
    • 8. Binding site for talin
    • 9. Transmembrane component
    • 10. Attach cell to basal lamina
    • 11. Combinations of integrins allows for differential signaling in that enironment
    • 12. Different cells express different combinations of integrins
    • 13. Different Cells have Different Expressions/Interactions of integrins
    • 14. A5B1
    • 15. Allows cells to interact with fibronectin
    • 16. Prime component of fibrillar macromolecules in the EXC Matrix below basal lamina
    • 17. A6B1
    • 18. Allows cells to interact with laminin
    • 19. Laminin is the basal lamina
    • 20. A7B1
    • 21. Muscle cells
    • 22. LFA
    • 23. White blood cells/immune cells of the blood
    • 24. Need to be able to move through endothelial cells, enter into tissue, bind to laminin and deal with infection at that site
    • 25. A6B4
    • 26. Allows epithelial cells to interact with basal lamina
    • 27. Can be targeted in disease states that result in blistering of skins b/c epithelial cells don’t attach well to basal lamina
    • 28. Mutations affect cells
    • 29. Beta1
    • 30. Embryo can’t implant because of the role of allowing embryo to develop
    • 31. Alpha7
    • 32. Different types of muscular dystrophy
    • 33. Beta2 or Alpha subunit of LFA
    • 34. WBC can’t migrate into tissue to deal with infections
    • 35. Leukocyte Adhesion Deficiencies
    • 36. Neutrophiles are the first WBC to move to infection, primary response to infection
    • 37. If no migration, infection has an increased chance of infecting host cells
    • 38. Focal Adhesions
    • 39. Assembled actin filaments and actin associated proteins and integrins
    • 40. A site where actin filaments assemble due to integrin receptors linked to actin binding proteins
    • 41. Focal adhesions are site that allow cell to adhere to EXC matrix
    • 42. Kinases that activate aseembly of focal adhesions
    • 43. Focal Adhesion Kinase (FAK)
    • 44. Turned on after integrin activation
    • 45. Drives deoplymerization actin and breakdown of focal adhesion
    • 46. In order for cells to be mobile, FA must first form but then be broken down. b/c if maintainted, the cell can’t move and stuck at that spot. Say break one at back and make one at front for movement
    • 47. Fibroblasts/immune cells/RBC and other mobile cells
    • 48. Integrin Receptor Kinase
    • 49. Help drive signaling at site of integrin acticvation and regulate what happens with actin filaments at that site
    • 50. Talin interacts with cytoplasmic regions of integrin receptors when bound to fibronectin (activated) or laminin
    • 51. Confo change occurs as integrins receptors are bound by ligand in EXC matrix
    • 52. Allows to interact with actin associate proteins like talin
    • 53. Alpha-Actinin
    • 54. Bind to growing actin filaments to organize them
    • 55. Generates parallel association as actin filaments begin to form
    • 56. Actin associated molecules are linked to signaling pathways like Ras, driving rate of assembly of actin filaments
    • 57. Hemidesmosomes
    • 58. Immobile cells
    • 59. Exists at basal membrane of epithelial cells (polarized, apical side where microvilli are, and basal side, near basal lamina)
    • 60. Basal lamina has embedded in it, fibrillar types of EXC matrix proteins, one being laminin
    • 61. Transmembrane integrin proteins links epithelial cell to proteins of EXC matrix
    • 62. A6B4 integrin is specifically found in hemisdesmosomes of epithelial cells
    • 63. Links with intermediate filaments
    • 64. This association organizes intermediate filaments in epithelial cells to help with tensile functions/mechanical stress functions of intermediate filaments
    • 65. Link to plectin proteins that associate with integrins, allowing them to link with intermediate filaments
    • 66. Plaque
    • 67. Made of plectin proteins
    • 68. Link with integrins
    • 69. BPAG
    • 70. Second type of transmembrane protein that binds to EXC matrix
    • 71. Doesn’t link to actin