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http://purl.uniprot.org/citations/17584991 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/17584991 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/17584991 | http://www.w3.org/2000/01/rdf-schema#comment | "Activation of group I metabotropic glutamate (mGlu) receptors recruits the endocannabinoid system to produce both short- and long-term changes in synaptic strength in many regions of the brain. Although there is evidence that the endocannabinoid 2-arachidonoylglycerol (2-AG) mediates this process, the molecular mechanism underlying 2-AG mobilization remains unclear. In the present study, we used a combination of genetic and targeted lipidomic approaches to investigate the role of the postsynaptic membrane-associated lipase, diacylglycerol lipase type-alpha (DGL-alpha), in mGlu receptor-dependent 2-AG mobilization. DGL-alpha overexpression in mouse neuroblastoma Neuro-2a cells increased baseline 2-AG levels. This effect was accompanied by enhanced utilization of the 2-AG precursor 1-stearoyl,2-arachidonoyl-sn-glycerol and increased accumulation of the 2-AG breakdown product arachidonic acid. A similar, albeit less marked response was observed with other unsaturated and polyunsaturated monoacylglycerols, 1,2-diacylglycerols, and fatty acids. Silencing of DGL-alpha by RNA interference elicited lipidomic changes opposite those of DGL-alpha overexpression and abolished group I mGlu receptor-dependent 2-AG mobilization. Coimmunoprecipitation and site-directed mutagenesis experiments revealed that DGL-alpha interacts, via a PPxxF domain, with the coiled-coil (CC)-Homer proteins Homer-1b and Homer-2, two components of the molecular scaffold that enables group I mGlu signaling. DGL-alpha mutants that do not bind Homer maintained their ability to generate 2-AG in intact cells but failed to associate with the plasma membrane. The findings indicate that DGL-alpha mediates group I mGlu receptor-induced 2-AG mobilization. They further suggest that the interaction of CC-Homer with DGL-alpha is necessary for appropriate function of this lipase."xsd:string |
http://purl.uniprot.org/citations/17584991 | http://purl.org/dc/terms/identifier | "doi:10.1124/mol.107.037796"xsd:string |
http://purl.uniprot.org/citations/17584991 | http://purl.org/dc/terms/identifier | "doi:10.1124/mol.107.037796"xsd:string |
http://purl.uniprot.org/citations/17584991 | http://purl.uniprot.org/core/author | "Zhu C."xsd:string |
http://purl.uniprot.org/citations/17584991 | http://purl.uniprot.org/core/author | "Zhu C."xsd:string |
http://purl.uniprot.org/citations/17584991 | http://purl.uniprot.org/core/author | "Mackie K."xsd:string |
http://purl.uniprot.org/citations/17584991 | http://purl.uniprot.org/core/author | "Mackie K."xsd:string |
http://purl.uniprot.org/citations/17584991 | http://purl.uniprot.org/core/author | "Wallace M."xsd:string |
http://purl.uniprot.org/citations/17584991 | http://purl.uniprot.org/core/author | "Wallace M."xsd:string |
http://purl.uniprot.org/citations/17584991 | http://purl.uniprot.org/core/author | "Astarita G."xsd:string |
http://purl.uniprot.org/citations/17584991 | http://purl.uniprot.org/core/author | "Astarita G."xsd:string |
http://purl.uniprot.org/citations/17584991 | http://purl.uniprot.org/core/author | "Piomelli D."xsd:string |
http://purl.uniprot.org/citations/17584991 | http://purl.uniprot.org/core/author | "Piomelli D."xsd:string |
http://purl.uniprot.org/citations/17584991 | http://purl.uniprot.org/core/author | "Jung K.M."xsd:string |
http://purl.uniprot.org/citations/17584991 | http://purl.uniprot.org/core/author | "Jung K.M."xsd:string |
http://purl.uniprot.org/citations/17584991 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
http://purl.uniprot.org/citations/17584991 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
http://purl.uniprot.org/citations/17584991 | http://purl.uniprot.org/core/name | "Mol. Pharmacol."xsd:string |
http://purl.uniprot.org/citations/17584991 | http://purl.uniprot.org/core/name | "Mol. Pharmacol."xsd:string |
http://purl.uniprot.org/citations/17584991 | http://purl.uniprot.org/core/pages | "612-621"xsd:string |
http://purl.uniprot.org/citations/17584991 | http://purl.uniprot.org/core/pages | "612-621"xsd:string |
http://purl.uniprot.org/citations/17584991 | http://purl.uniprot.org/core/title | "A key role for diacylglycerol lipase-alpha in metabotropic glutamate receptor-dependent endocannabinoid mobilization."xsd:string |
http://purl.uniprot.org/citations/17584991 | http://purl.uniprot.org/core/title | "A key role for diacylglycerol lipase-alpha in metabotropic glutamate receptor-dependent endocannabinoid mobilization."xsd:string |