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Prof. Dermot Cooper - University of Cambridge, UK Dermot Cooper obtained his PhD in biochemistry from Bangor in the UK. He spent five postdoctoral years with Martin Rodbell at NIH before establishing his lab in Denver, Colorado. In 2002 he moved to the University of Cambridge. Dr. Cooper has had a long-standing interest in adenylyl cyclases, particularly in their regulation by Calcium, both in terms of the structural characteristics that confer susceptibility to Calcium in vitro and the cellular features that ensure regulation in the intact cell. The dynamic regulation of adenylyl cyclases by Calcium have led inevitably into unraveling the dynamics of cAMP in single cells.
Talk Online Publication: Oct 2007 How to cite this talk:
Cooper, D. (2007), "Calcium-Regulated Adenylyl Cyclases and Cyclic AMP Compartmentalization", in Simpson, A. (ed.), Calcium Signaling: Regulation, Mechanisms, Effectors, Role in Disease and Recent Advances, The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (online at http://hstalks.com/bio)
Direct talk access link:
http://hstalks.com/lib.php?t=HST29.1368_1_2&c=252
TOPICS COVERED IN CALCIUM-REGULATED ADENYLYL CYCLASES AND CYCLIC AMP COMPARTMENTALIZATION Calcium-entry | Elements of the compartment: adenylyl cyclases, lipid rafts, PP2A, NHE1, calmodulin and PDE | cAMP kinetics within the compartment in single cells: role of PDE4, PKA and AKAPs | cAMP oscillations
1. Introduction
2. Ca2+ and cAMP: two major 2nd messengers
3. Outline
4. Ca2+ sensitivities of adenylyl cyclases in vitro
5. Adenylyl cyclase type 8 (AC8)
6. Ca2+ sensitivities of adenylyl cyclases in vitro
7. In vitro regulation by Ca2+ is mimicked
8. Capacitative Ca2+-entry
9. Ca2+-regulation of ACs is selective for CCE
10. Capacitative Ca2+ entry exclusively activates AC8
11. Adenylyl cyclases and CCE channels colocalize
12. Ca2+-sensitive cyclases are enriched in lipid rafts
13. Cyclase localization in caveolae/rafts
14. Regulation/localization of ACs
15. Cyclase presence in rafts
16. Probing of cyclase raft-targeting
17. Cyclese trafficking to plasma membrane
18. Role of TM vs. cytosolic domains
19. Hypothetical calcium signal-coupling domain
20. Structure of K ATP channel
21. Roles of the N-terminus of AC8
22. Calmodulin binding sites
23. Essential component of responsivness to CCE
24. 2nd role for AC8 N-terminus binding of PP2A
25. Another element of the AC microdomain
26. pH sensitivity of Ca-sensitive Acs
27. Effect of modest in vitro pH changes
28. Global pH changes don't affect stimulation of AC8
29. Global pH changes don't affect stimulation of AC6
30. NHE1 activity minimizes the effects of weak acid
31. NHE1 is located in lipid rafts
32. NHE1 and ACs
33. Microdomains of cAMP
34. Agonist evoked cAMP changes
35. Phosphodiesterase activity
36. Anchoring proteins regulate cAMP dynamics
37. Questions about AKAP and PDE4
38. Candidate membrane-associated AKAPs
39. RNAi of candidate AKAPs
40. Co-immunoprecipitation of gravin with PDE4D
41. Signalling module in HEK 293 cells
42. The interplay between Ca2+ and cAMP signals
43. CCE-induced stimulation of AC8 activity
44. Synchronous Ca2+ and cAMP oscillations
45. Recovery from Ca2+-evoked cAMP changes
46. Agonist-induced oscillations in Ca2+ and cAMP
47. Sequence of events that drive cAMP oscillations
48. What constitutes a microdomain for cAMP or AC?
49. The cAMP microdomain
50. Conclusions
51. The key supporting players
52. END
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