title: Calcium-dependent increases in protein kinase-A activity in mouse retinal ganglion cells are mediated by multiple adenylate cyclases.
abstract: 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.
authors.affiliation: Neurobiology Section, Division of Biological Sciences, University of California San Diego, La Jolla, California, USA.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Dunn
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Storm
authors.forename: Marla B
authors.initials: MB
authors.lastname: Feller
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D012160:Retina / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism*
chemical_list: D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D010727:Phosphoric Diester Hydrolases; D000262:Adenylyl Cyclases; D002118:Calcium