3.15.2010 – Cell Signaling<br /><ul><li>Dictostylium - Cyclic AMP
We will look at signaling molecules that are:
Membrane bound
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3.15.2010

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3.15.2010

  1. 1. 3.15.2010 – Cell Signaling<br /><ul><li>Dictostylium - Cyclic AMP
  2. 2. We will look at signaling molecules that are:
  3. 3. Membrane bound
  4. 4. Secreted
  5. 5. Form the basis for cell communication, such as long distance or shorter and remote
  6. 6. Direct cell contact communication
  7. 7. Cells must be able to decipher the signals
  8. 8. Slide 2 – different types of cell signaling
  9. 9. Endocrine
  10. 10. Circulate in the blood, long distances
  11. 11. Paracrine – short distance, local
  12. 12. Steroid horomones where a molecule is secreted into EX space, but traveling short distances
  13. 13. Local mediators
  14. 14. Amino acids
  15. 15. Lipids
  16. 16. Growth factors (huge family of proteins)
  17. 17. Cytokines
  18. 18. Growth/survival/cell proliferation etc
  19. 19. The response is the specific signaling aspect of this process, which lies with the receptors on a cell.
  20. 20. Neuronal
  21. 21. Neurotransmitters are the soluble cues that are released
  22. 22. Excitatory Neurotransmitter
  23. 23. Glutamate
  24. 24. Inhibitory Neuro.
  25. 25. GABA – derived from glutamate
  26. 26. Decreases excitation at
  27. 27. Neuronal signaling
  28. 28. Presynaptic cell releases the neurotransmitter (chemical cues)
  29. 29. Into the synaptic cleft (space between presynaptic cell and target cell)
  30. 30. Postsynaptic cell is the receiver
  31. 31. Synapse – structure made up by precell/postcell/syna cleft
  32. 32. Contact Dependent Intracellular Signaling
  33. 33. Don’t secrete but use membrane bound cues to interact with receptor on target cell.
  34. 34. Notch/Delta – heterophylic binding (two different structures binding to one another
  35. 35. Important in early development
  36. 36. Integrins/CAM (cell adhesion molecules) – heterophylic binding
  37. 37. Important in development and allow cells to attach to endothelial cells
  38. 38. Cadherin/Cadherin – Homophylic binding, requires calcium
  39. 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. 40. Slide 3
  41. 41. Transmembrane receptor binding to a hydrophilic soluble signal (don’t go through membrane)
  42. 42. In order for molecule to have an effect on a cell, must bind to receptor and causes a
  43. 43. Receptor mediated endocytosis
  44. 44. Intracellular Receptors
  45. 45. Nucleus
  46. 46. Cytoplasm
  47. 47. Bind to small, hydrophobic molecules such as steroids.
  48. 48. Sometimes move to nucleus and regulate gene transcription
  49. 49. Gases can exist as signaling transduction molecules
  50. 50. CO – carbon monoxide
  51. 51. Nitric Oxide – NO
  52. 52. Receptors bind gas
  53. 53. Slide 4
  54. 54. Series of events that happens
  55. 55. Must have receptor bind signal transduction molecule (
  56. 56. Induces conformational change that is linked directly to receptor or neighboring component
  57. 57. Signal transduction components for amplification
  58. 58. Cellular response
  59. 59. Change in cytoskeleton
  60. 60. Changes in gene transcription
  61. 61. Response of receptors
  62. 62. Increase survival
  63. 63. Induce cell death
  64. 64. Receptors
  65. 65. Differential Expression/Exocytosis
  66. 66. Receptor Mediated Endocytosis
  67. 67. Receptors can be modified even as they are expressed in plasma membrane
  68. 68. Phosphorylation is common!
  69. 69. Can activate receptor or make it inactive
  70. 70. Acts as a switch (turn things on and off)
  71. 71. Signaling molecules that bind receptors can be modified as well
  72. 72. Phosphorylation
  73. 73. Bound by inhibitory proteins
  74. 74. Bound to GTP or GDP
  75. 75. Slide 5 – Examples of small hydrophobic signaling molecules
  76. 76. How peripheral nervous system regulates dilation
  77. 77. Allows endothelial cells to respond to signals in peripheral nervous sytem
  78. 78. Smooth muscles cells will relax to become loose allowing blood vessels to dilate (become larger)
  79. 79. Sympathetic neurons
  80. 80. Secretion of neurontransmitter called acetylcholine
  81. 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. 82. Nerve
  83. 83. NOS – nitric oxide synthase drives the reaction where you convert arginie to nitric oxide, activated by binding of acetylcholine to acetylcholine receptor
  84. 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. 85. Smooth muscle cells have a recptor for NO gas, which binds to NO and indices relaxation of smooth muscle.

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