1. Last Class 1. GPCR signaling: 2. Enzyme-linked Receptor signaling:
PKA and Calcium
2. Enzyme-linked Receptor signaling:
RTK->Ras and PI3K
3. Proteolysis-mediated signaling pathways
NF-KB pathway

2. The Cytoskeleton

3. Cytoskeletal Filaments Microtubules: intracellular traffic
Actin Filaments: cell shape and locomotion
Intermediate Filaments: mechanical strength

4. Cytoskeleton and changes in cell shape

5. Multi-filament formation of cytoskeletal filaments

6. Actin Monomers and Filaments

7. The Time Courses of Actin Polymerization

8. The treadmilling of an actin filament

9. Microtubules

10. Microtubules: Plus end and Minus end
Dynamic Instability

11. Microtubules: Plus end and Minus end Experimental Recording

12. Microtubules: Dynamic Instability

13. Microtubules: GDP-bound and bending

14. Microtubules: GDP-bound and bending

15. Intermediate Filaments

16. Intermediate Filaments
Coiled coil formation

17. Intermediate Filaments
Difficult to break

18. Mutation of Keratin (one kind of intermediate filament) gene causes skin blistering

20. Cytoskeletal Regulation

21. Microtubules

22. g-tubulin nucleation for microtubule polymerization

23. Centrosome and Microtubule Network (movie)

24. Centrosome and its center-seeking function (movie: MT-red and ER-green)

25. Microtubules can find its center

26. Stathmin on Microtubule depolymerization
(sequestering)

27. Katanin on Microtubule depolymerization
cleavage

28. Protein binding and the effects on microtubule stability (movie, MT binding proteins and dynamics)

29. Organization of Microtubule bundles
MAP: microtubule associated protein

30. Actin Filaments

31. Actin Filament Regulation occurs at plasma membrane
Green: Phalloidin staining of existing actin fibers
Red: new actin filaments incorporating rhodamine actin

32. ARP proteins and actin nucleation

33. ARP proteins and actin nucleation

34. Profilin and Thymosin on Actin polymerization

35. Profilin and Thymosin on Actin polymerization

36. Cofilin on Actin Depolymerization

37. Gelsolin severs actin filaments

38. Platelet Activation

39. Capping and Stability

40. Different Actin Arrays in a cell Bundles and gel-like networks

41. Actin Cross-Linking Proteins
Bundles: Fimbrin: filopodia; a-actinin: stress fibers
Gel-like network: spectrin and filamin

42. Different Bundles with different cross-linking Proteins

43. ERM Linking Actin to Plasma Membrane (ezrin, radixin, moesin)

44. Actin Filaments and Cellular functions
Focal Adhesions

45. Actin Filaments Regulations

46. Molecular Motors

47. Myosins (movie: heart contraction)

48. Motor Activity of Myosin Heads

49. Myosin Structural Changes walking along an actin filament

51. Movie: summarize actomyosin contraction cycle

52. Skeletal Muscle Cell, myoblasts

53. Skeletal Muscle Myofibrils

54. Sliding Acto-Myosin filaments

55. Protein Structures of Sarcomere Tropomodulin/troponin: minus end
Z-disc/a-actinin: plus end

56. T-tubules and sarcoplasmic reticulum

57. Calcium/Troponin and skeletal muscle contraction
T, I, C subunits of troponin: tropomyosin binding, inhibitory, calcium binding

58. Regulation of Myosin

59. Kinesin and dynein bind to microtubules
Kinesin and Myosin
Kinesin and dynein bind to microtubules

61. Kinesin: - to +; Dynein: + to –
Both on microtubules (movie, MT transportation)

62. Cell Behaviors and Cytoskeleton

63. Cell Migration Model

64. Migratory Keratocytes

65. Lamellipodial Fragments
Blue: Actin
Pink: myosin II

66. ARP protein and Lamellipodia: Actin: Red
ARP: Green

67. Lamellipodial Fragments
Actin: Red
Cofilin: Green

68. Traction forces on the substratum

69. Chemotaxis and Polarization External signals can control cell behavior

70. Summary 1. Cytoskeleton components:
Microtubules
Actin Filaments
Intermediate Filaments
2. The regulation of microtubules and Actin
filaments
3. Molecular Motors
4. Cell behaviors related to cytoskeleton