4.16.2010 lecture 2

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4.16.2010 lecture 2

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

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