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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Public Library of Science (PLoS)
2009-11-01
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| 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. |
| format | Article |
| id | doaj-art-8f088b879d9044d88868d37e33e2b3fe |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2009-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| 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 |
| work_keys_str_mv | AT timothyadunn calciumdependentincreasesinproteinkinaseaactivityinmouseretinalganglioncellsaremediatedbymultipleadenylatecyclases AT danielrstorm calciumdependentincreasesinproteinkinaseaactivityinmouseretinalganglioncellsaremediatedbymultipleadenylatecyclases AT marlabfeller calciumdependentincreasesinproteinkinaseaactivityinmouseretinalganglioncellsaremediatedbymultipleadenylatecyclases |