2. We will look at signaling molecules that are:

3. Membrane bound

4. Secreted

5. Form the basis for cell communication, such as long distance or shorter and remote

6. Direct cell contact communication

7. Cells must be able to decipher the signals

8. Slide 2 – different types of cell signaling

9. Endocrine

10. Circulate in the blood, long distances

11. Paracrine – short distance, local

12. Steroid horomones where a molecule is secreted into EX space, but traveling short distances

13. Local mediators

14. Amino acids

15. Lipids

16. Growth factors (huge family of proteins)

17. Cytokines

18. Growth/survival/cell proliferation etc

19. The response is the specific signaling aspect of this process, which lies with the receptors on a cell.

20. Neuronal

21. Neurotransmitters are the soluble cues that are released

22. Excitatory Neurotransmitter

23. Glutamate

24. Inhibitory Neuro.

25. GABA – derived from glutamate

26. Decreases excitation at

27. Neuronal signaling

28. Presynaptic cell releases the neurotransmitter (chemical cues)

29. Into the synaptic cleft (space between presynaptic cell and target cell)

30. Postsynaptic cell is the receiver

31. Synapse – structure made up by precell/postcell/syna cleft

32. Contact Dependent Intracellular Signaling

33. Don’t secrete but use membrane bound cues to interact with receptor on target cell.

34. Notch/Delta – heterophylic binding (two different structures binding to one another

35. Important in early development

36. Integrins/CAM (cell adhesion molecules) – heterophylic binding

37. Important in development and allow cells to attach to endothelial cells

38. Cadherin/Cadherin – Homophylic binding, requires calcium

39. Secreted, soluble signals from a cell that are probably processed in lumen of ER and trafficked to PM and released into EX space, or circulation and travel long distances, endocrine.

40. Slide 3

41. Transmembrane receptor binding to a hydrophilic soluble signal (don’t go through membrane)

42. In order for molecule to have an effect on a cell, must bind to receptor and causes a

43. Receptor mediated endocytosis

44. Intracellular Receptors

45. Nucleus

46. Cytoplasm

47. Bind to small, hydrophobic molecules such as steroids.

48. Sometimes move to nucleus and regulate gene transcription

49. Gases can exist as signaling transduction molecules

50. CO – carbon monoxide

51. Nitric Oxide – NO

52. Receptors bind gas

53. Slide 4

54. Series of events that happens

55. Must have receptor bind signal transduction molecule (

56. Induces conformational change that is linked directly to receptor or neighboring component

57. Signal transduction components for amplification

58. Cellular response

59. Change in cytoskeleton

60. Changes in gene transcription

61. Response of receptors

62. Increase survival

63. Induce cell death

64. Receptors

65. Differential Expression/Exocytosis

66. Receptor Mediated Endocytosis

67. Receptors can be modified even as they are expressed in plasma membrane

68. Phosphorylation is common!

69. Can activate receptor or make it inactive

70. Acts as a switch (turn things on and off)

71. Signaling molecules that bind receptors can be modified as well

72. Phosphorylation

73. Bound by inhibitory proteins

74. Bound to GTP or GDP

75. Slide 5 – Examples of small hydrophobic signaling molecules

76. How peripheral nervous system regulates dilation

77. Allows endothelial cells to respond to signals in peripheral nervous sytem

78. Smooth muscles cells will relax to become loose allowing blood vessels to dilate (become larger)

79. Sympathetic neurons

80. Secretion of neurontransmitter called acetylcholine

81. Peripheral Nervous System Sympathetic Neuron releases acetylcholine to its receptor that is in the endothelial cell, which makes up blood vessel wall lining (interior of vessel)

82. Nerve

83. NOS – nitric oxide synthase drives the reaction where you convert arginie to nitric oxide, activated by binding of acetylcholine to acetylcholine receptor

84. NO as made, is rapidly lost so diffusion can carry NO away, and binds to receptor in target cell that accepts it. (diffuses across membrane)

85. Smooth muscle cells have a recptor for NO gas, which binds to NO and indices relaxation of smooth muscle.