Calcium-Dependent Increases in Protein Kinase-A Activity in Mouse Retinal Ganglion Cells Are Mediated by Multiple Adenylate Cyclases

被引:41
作者
Dunn, Timothy A.
Storm, Daniel R.
Feller, Marla B.
机构
[1] Neurobiology Section, Division of Biological Sciences, University of California San Diego, La Jolla, CA
[2] Department of Pharmacology, University of Washington, Seattle, WA
[3] Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, CA
来源
PLOS ONE | 2009年 / 4卷 / 11期
关键词
BARREL MAP DEVELOPMENT; ELECTRICAL-ACTIVITY; SUBCELLULAR DYNAMICS; RETINOTOPIC MAP; SPERM-MOTILITY; CYCLIC-AMP; RAT RETINA; GROWTH; REFINEMENT; CAMP;
D O I
10.1371/journal.pone.0007877
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Neurons undergo long term, activity dependent changes that are mediated by activation of second messenger cascades. In particular, calcium-dependent activation of the cyclic-AMP/Protein kinase A signaling cascade has been implicated in several developmental processes including cell survival, axonal outgrowth, and axonal refinement. The biochemical link between calcium influx and the activation of the cAMP/PKA pathway is primarily mediated through adenylate cyclases. Here, dual imaging of intracellular calcium concentration and PKA activity was used to assay the role of different classes of calcium-dependent adenylate cyclases (ACs) in the activation of the cAMP/PKA pathway in retinal ganglion cells (RGCs). Surprisingly, depolarization-induced calcium-dependent PKA transients persist in barrelless mice lacking AC1, the predominant calcium-dependent adenylate cyclase in RGCs, as well as in double knockout mice lacking both AC1 and AC8. Furthermore, in a subset of RGCs, depolarization-induced PKA transients persist during the inhibition of all transmembrane adenylate cyclases. These results are consistent with the existence of a soluble adenylate cyclase that plays a role in calcium-dependent activation of the cAMP/PKA cascade in neurons.
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页数:9
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