1. Last Class: 1. transportation at the plasma membrane A. carrier protein, B. channel protein 2. intracellular compartments A. nucleus, B. Endoplasmic Reticulum

2. Intracellular Vesicular Traffic

3. The endocytic and biosynthetic-secretory pathways

4. Vesicular transport

5. The intracellular compartments of the eucaryotic cell in the biosynthetic-secretory and endocytic pathways

6. Utilization of different coats in vesicular traffic

7. Clathrin-coated pits and vesicles

8. The structure of a clathrin coat

9. The assembly and disassembly of a clathrin coat

10. The role of dynamin in pinching off clathrin-coated vesicles from the membrane Shibire mutant in drosophila

11. A current model of COPII-coated vesicle formation

12. The postulated role of SNAREs in guiding vesicular transport

13. The structure of paired snare

14. A model for how SNARE proteins may concentrate in membrane fusion

15. Dissociation of SNARE pairs by NSF after a membrane fusion cycle is completed

17. A postulated role of Rab protein in facilitating the docking of transport vesicles

18. The entry of enveloped viruses into cells

19. Transport from the ER through the Golgi apparatus

20. The recruitment of cargo molecules into ER transport vesicles

21. Retention of incompletely assembled antibody molecules in the ER

22. Vesicular tubular clusters

23. A model for the retrieval of ER resident proteins

24. The Golgi apparatus

25. The functional compartmentalization of the Golgi apparatus Notice of multiple steps involving glycosylation

26. Two possible models explaining the organization of the Golgi apparatus and the transport of proteins from one cisterna to the next

27. Transport from the trans Golgi nextwork to Lysosomes

28. Lysosomes Low pH Full of Acid hydrolases

29. The structure of mannose 6-phosphate on a lysosome enzyme

30. The transport of newly synthesized lysosomal hydrolases to lysosomes

31. Transport into the cell from the plasma membrane endocytosis

32. Phagocytosis by a macrophage Phagocytosis: large particle, >250nm Pinocytosis: fluid, liquid, 100 nm One macrophage and two red blood cells

33. The formation of clathrin- coated vesicles from the plasma membrane

34. Caveolae in the plasma membrane of a fibroblast

35. A low-density lipoprotein (LDL) particle

36. Normal and mutant LDL receptor

37. The receptor-mediated endocytosis of LDL

38. Possible fates for transmembrane receptor proteins that have been endocytosed

39. Storage of plasma membrane proteins in recycling endosomes

40. Transcytosis

41. Sorting of membrane proteins in the endocytic pathway Green: EGF-EGFR Red: transferrin and its receptor

42. The sequestration of endocytosed proteins into internal membranes of multivesicular bodies

43. Transport from the trans Golgi network to the cell exterior: exocytosis

44. The constitutive and regulated secretory pathways

45. The three best-understood pathways of protein sorting in the trans Golgi network

46. Exocytosis of secretory vesicles

47. Electron micrographs of exocytosis in rat mast cells Release of histamine

48. Exocytosis as a localized responses Beads attachment localized the release

49. Model of lipid rafts in the trans Golgi network

50. The formation of synaptic vesicles

51. Summary Intracellular vesicular traffic, SNARE, GAB, Clathrin, Dynamin, Adaptin ER->Golgi, COPII, COPI Golgi->lysosome, acid hydrolases, M6P endocytosis, phagocytosis, pinocytosis, clathrin-coated pit, caveolae, Exocytosis, constitutive and regulated mechanisms

52. Cell Signaling 1: General Concepts

53. A simple intracellular signaling pathway

54. Extracellular signaling molecules bind to receptors

55. Signals can be tranmitted either short or long distances (I)

56. Signals can be tranmitted either short or long distances (II)

57. For Long distance, two typical ways Endocrine signaling Different cells need specific ligands and receptors

58. Synaptic signaling More efficient, same set of ligands and receptors

59. Signaling via GAP Junctions No ligand-receptor system needed

60. Combinatory effect of multiple inputs

61. Different receptor type and intracellular signaling molecules determine the ultimate response

62. Many signaling molecules have short lifetime

63. NO (nitric oxide) induces the relaxation of SMC The function of viagra is to inhibit cyclic GMP phosphodiesterase, hence elongate the lifetime of cyclic GMP and relaxation

64. 2 steps of responses may occur upon stimulation Secon

65. Cell Surface receptors belong to three classes: 1. ion-channel-linked receptors, 2. G-protein-linked receptors, 3. enzyme-linked receptors

67. Different Kinds of intracellular proteins serving as signaling molecules 1.Relay proteins 2.Messenger proteins 3.Adaptor proteins 4.Amplifier proteins 5.Transducer proteins 6.Bifurcation proteins 7.Integrator proteins 8.Latent gene regulatory proteins

68. Two kinds of molecule switch events Phosphorylation and GTP binding

69. Signaling integration

70. Intracellular signaling complexes enhance the speed, efficiency, and specificity 2 types: Preassembled vs. Assembled after stimulation

71. Intracellular signaling complexes enhance the speed, efficiency, and specificity 2 types: Preassembled vs. Assembled after stimulation

72. Binding domains for interactions between proteins and complex assembly

73. Cells can be sensitive to subtle difference in environment 1. Multiple ligands are needed for one signaling molecule

74. Cells can be sensitive to subtle difference in environment 2. Multiple ligated molecules are needed to be assembled to be functional

75. Cells can be sensitive to subtle difference in environment 3. Positive feedback can enhance the response drastically

76. Cells can adjust their sensitivity to stimuli by desensitization process

77. Summary Typical signaling transduction pathway: 1. ligand- receptor, 2. gap junctions Different inputs, receptors, intracellular signaling network determine the ultimate response The importance of lifetime of molecules Different steps of responses The types of receptors: ion-channel-linked, G protein coupled, enzyme-linked receptors Intracellular signaling molecules, signaling switches, signaling integration, signaling complex assembly, protein-protein binding modulus, signaling amplification, signaling desensitization