title: Diacylglycerol signaling underlies astrocytic ATP release.
abstract: 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.
authors.affiliation: Department of Neuroscience, Tufts University, 136 Harrison Avenue, Boston, MA 02111, USA. mungenas@mit.edu
authors.forename: Alison E
authors.initials: AE
authors.lastname: Mungenast
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D004075:Diglycerides / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology; D017930:Genes, Reporter; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000235:genetics; D011493:Protein Kinase C / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D004075:Diglycerides; D007202:Indicators and Reagents; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D018047:Receptors, Purinergic P1; C503321:Unc13a protein, mouse; D000255:Adenosine Triphosphate; D008156:Luciferases; D011493:Protein Kinase C