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dc.contributor.authorKantamneni, Sriharsha*
dc.contributor.authorGonzàlez-Gonzàlez, I.M.*
dc.contributor.authorLuo, J.*
dc.contributor.authorCimarosti, H.*
dc.contributor.authorJacobs, S.C.*
dc.contributor.authorJaafari, N.*
dc.contributor.authorHenley, J.M.*
dc.date.accessioned2016-04-13T15:54:32Z
dc.date.available2016-04-13T15:54:32Z
dc.date.issued2014-01-14
dc.identifier.citationKantamneni S, Gonzàlez-Gonzàlez IM, Luo J et al (2014) Differential regulation of GABAB receptor trafficking by different modes of N-methyl-D-aspartate (NMDA) receptor signaling. The Journal of Biological Chemistry. 289(10): 6681-6694.en_US
dc.identifier.urihttp://hdl.handle.net/10454/8125
dc.descriptionyesen_US
dc.description.abstractInhibitory GABAB receptors (GABABRs) can down-regulate most excitatory synapses in the CNS by reducing postsynaptic excitability. Functional GABABRs are heterodimers of GABAB1 and GABAB2 subunits and here we show that the trafficking and surface expression of GABABRs is differentially regulated by synaptic or pathophysiological activation of NMDA receptors (NMDARs). Activation of synaptic NMDARs using a chemLTP protocol increases GABABR recycling and surface expression. In contrast, excitotoxic global activation of synaptic and extrasynaptic NMDARs by bath application of NMDA causes the loss of surface GABABRs. Intriguingly, exposing neurons to extreme metabolic stress using oxygen/glucose deprivation (OGD) increases GABAB1 but decreases GABAB2 surface expression. The increase in surface GABAB1 involves enhanced recycling and is blocked by the NMDAR antagonist AP5. The decrease in surface GABAB2 is also blocked by AP5 and by inhibiting degradation pathways. These results indicate that NMDAR activity is critical in GABABR trafficking and function and that the individual subunits can be separately controlled to regulate neuronal responsiveness and survival.en_US
dc.description.sponsorshipBBSRC, MRC and the European Research Councilen_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://dx.doi.org/10.1074/jbc.M113.487348en_US
dc.rights© 2014 American Society for Biochemistry and Molecular Biology. Reproduced in accordance with the publisher's self-archiving policy.en_US
dc.subjectChem-LTP; G Protein-coupled Receptors (GPCR); GABA Receptors; GABAB Receptor; Glutamate Receptor Ionotropic (AMPA, NMDA); Neurodegeneration; Neurotransmitter Receptors; Oxygen-glucose Deprivation (OGD); Receptor Endocytosis; Receptor Recyclingen_US
dc.titleDifferential regulation of GABAB receptor trafficking by different modes of N-methyl-D-aspartate (NMDA) receptor signalingen_US
dc.status.refereedYesen_US
dc.date.Accepted2013-12-24
dc.typeArticleen_US
dc.type.versionPublished versionen_US


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