title: Phospho-dependent Accumulation of GABABRs at Presynaptic Terminals after NMDAR Activation.
abstract: Here, we uncover a mechanism for regulating the number of active presynaptic GABAB receptors (GABABRs) at nerve terminals, an important determinant of neurotransmitter release. We find that GABABRs gain access to axon terminals by lateral diffusion in the membrane. Their relative accumulation is dependent upon agonist activation and the presence of the two distinct sushi domains that are found only in alternatively spliced GABABR1a subunits. Following brief activation of NMDA receptors (NMDARs) using glutamate, GABABR diffusion is reduced, causing accumulation at presynaptic terminals in a Ca(2+)-dependent manner that involves phosphorylation of GABABR2 subunits at Ser783. This signaling cascade indicates how synaptically released glutamate can initiate, via a feedback mechanism, increased levels of presynaptic GABABRs that limit further glutamate release and excitotoxicity.
authors: Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
authors: Saad
authors: S
authors: Hannan
authors: Biologie Cellulaire de la Synapse, Inserm U1024, Institute of Biology, École Normale Supérieure (ENS), 46 rue d'Ulm, Paris 75005, France.
authors: Kim
authors: K
authors: Gerrow
authors: Biologie Cellulaire de la Synapse, Inserm U1024, Institute of Biology, École Normale Supérieure (ENS), 46 rue d'Ulm, Paris 75005, France.
authors: Antoine
authors: A
authors: Triller
authors: Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. Electronic address: t.smart@ucl.ac.uk.
authors: Trevor G
authors: TG
authors: Smart
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004058:Diffusion; D004622:Embryo, Mammalian; D025461:Feedback, Physiological; D015870:Gene Expression; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000033:anatomy & histology / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D020239:Receptor Cross-Talk; D018080:Receptors, GABA-B / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D009435:Synaptic Transmission; D046509:Tissue Culture Techniques; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology
chemical_list: D021122:Protein Subunits; D018080:Receptors, GABA-B; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D002118:Calcium
keywords: AMPK; Ca(2+) signaling; GABA receptors; GABA(B) receptors; NMDA receptors; bungarotoxin binding site; excitotoxicity; glutamate receptors; hippocampus; homeostatic signaling; lateral diffusion; phosphorylation; presynaptic terminal; quantum dots; receptor mobility; single-particle tracking; sushi domains