Calcium-dependent increases in protein kinase-A activity in mouse retinal ganglion cells are mediated by multiple adenylate cyclases.

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...

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Main Authors: Timothy A Dunn, Daniel R Storm, Marla B Feller
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-11-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0007877&type=printable
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author Timothy A Dunn
Daniel R Storm
Marla B Feller
author_facet Timothy A Dunn
Daniel R Storm
Marla B Feller
author_sort Timothy A Dunn
collection DOAJ
description 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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spelling doaj-art-8f088b879d9044d88868d37e33e2b3fe2025-08-20T02:01:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-11-01411e787710.1371/journal.pone.0007877Calcium-dependent increases in protein kinase-A activity in mouse retinal ganglion cells are mediated by multiple adenylate cyclases.Timothy A DunnDaniel R StormMarla B FellerNeurons 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0007877&type=printable
spellingShingle Timothy A Dunn
Daniel R Storm
Marla B Feller
Calcium-dependent increases in protein kinase-A activity in mouse retinal ganglion cells are mediated by multiple adenylate cyclases.
PLoS ONE
title Calcium-dependent increases in protein kinase-A activity in mouse retinal ganglion cells are mediated by multiple adenylate cyclases.
title_full Calcium-dependent increases in protein kinase-A activity in mouse retinal ganglion cells are mediated by multiple adenylate cyclases.
title_fullStr Calcium-dependent increases in protein kinase-A activity in mouse retinal ganglion cells are mediated by multiple adenylate cyclases.
title_full_unstemmed Calcium-dependent increases in protein kinase-A activity in mouse retinal ganglion cells are mediated by multiple adenylate cyclases.
title_short Calcium-dependent increases in protein kinase-A activity in mouse retinal ganglion cells are mediated by multiple adenylate cyclases.
title_sort calcium dependent increases in protein kinase a activity in mouse retinal ganglion cells are mediated by multiple adenylate cyclases
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0007877&type=printable
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AT danielrstorm calciumdependentincreasesinproteinkinaseaactivityinmouseretinalganglioncellsaremediatedbymultipleadenylatecyclases
AT marlabfeller calciumdependentincreasesinproteinkinaseaactivityinmouseretinalganglioncellsaremediatedbymultipleadenylatecyclases