Diacylglycerol Signaling Underlies Astrocytic ATP Release

Astrocytes have the ability to modulate neuronal excitability and synaptic transmission by the release of gliotransmitters. The importance of ATP released downstream of the activation of Gq-coupled receptors has been well established, but the mechanisms by which this release is regulated are unclear...

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Main Author: Alison E. Mungenast
Format: Article
Language:English
Published: Wiley 2011-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2011/537659
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author Alison E. Mungenast
author_facet Alison E. Mungenast
author_sort Alison E. Mungenast
collection DOAJ
description Astrocytes have the ability to modulate neuronal excitability and synaptic transmission by the release of gliotransmitters. The importance of ATP released downstream of the activation of Gq-coupled receptors has been well established, but the mechanisms by which this release is regulated are unclear. The current work reveals that the elevation of diacylglycerol (DAG) in astrocytes induces vesicular ATP release. Unexpectedly, DAG-induced ATP release was found to be independent of PKC activation, but dependent upon activation of a C1 domain-containing protein. Astrocytes express the C1 domain-containing protein Munc13-1, which has been implicated in neuronal transmitter release, and RNAi-targeted downregulation of Munc13-1 inhibits astrocytic ATP release. These studies demonstrate that elevations of DAG induce the exocytotic release of ATP in astrocytes, likely via a Munc13-1-dependent mechanism.
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spelling doaj-art-9c2e198720d84bdbacf977146ee305522025-08-20T02:20:16ZengWileyNeural Plasticity2090-59041687-54432011-01-01201110.1155/2011/537659537659Diacylglycerol Signaling Underlies Astrocytic ATP ReleaseAlison E. Mungenast0Department of Neuroscience, Tufts University, 136 Harrison Avenue, Boston, MA 02111, USAAstrocytes have the ability to modulate neuronal excitability and synaptic transmission by the release of gliotransmitters. The importance of ATP released downstream of the activation of Gq-coupled receptors has been well established, but the mechanisms by which this release is regulated are unclear. The current work reveals that the elevation of diacylglycerol (DAG) in astrocytes induces vesicular ATP release. Unexpectedly, DAG-induced ATP release was found to be independent of PKC activation, but dependent upon activation of a C1 domain-containing protein. Astrocytes express the C1 domain-containing protein Munc13-1, which has been implicated in neuronal transmitter release, and RNAi-targeted downregulation of Munc13-1 inhibits astrocytic ATP release. These studies demonstrate that elevations of DAG induce the exocytotic release of ATP in astrocytes, likely via a Munc13-1-dependent mechanism.http://dx.doi.org/10.1155/2011/537659
spellingShingle Alison E. Mungenast
Diacylglycerol Signaling Underlies Astrocytic ATP Release
Neural Plasticity
title Diacylglycerol Signaling Underlies Astrocytic ATP Release
title_full Diacylglycerol Signaling Underlies Astrocytic ATP Release
title_fullStr Diacylglycerol Signaling Underlies Astrocytic ATP Release
title_full_unstemmed Diacylglycerol Signaling Underlies Astrocytic ATP Release
title_short Diacylglycerol Signaling Underlies Astrocytic ATP Release
title_sort diacylglycerol signaling underlies astrocytic atp release
url http://dx.doi.org/10.1155/2011/537659
work_keys_str_mv AT alisonemungenast diacylglycerolsignalingunderliesastrocyticatprelease