title: mGluR long-term depression regulates GluA2 association with COPII vesicles and exit from the endoplasmic reticulum.
abstract: mGluR long-term depression (mGluR-LTD) is a form of synaptic plasticity induced at excitatory synapses by metabotropic glutamate receptors (mGluRs). mGluR-LTD reduces synaptic strength and is relevant to learning and memory, autism, and sensitization to cocaine; however, the mechanism is not known. Here we show that activation of Group I mGluRs in medium spiny neurons induces trafficking of GluA2 from the endoplasmic reticulum (ER) to the synapse by enhancing GluA2 binding to essential COPII vesicle proteins, Sec23 and Sec13. GluA2 exit from the ER further depends on IP3 and Ryanodine receptor-controlled Ca2+release as well as active translation. Synaptic insertion of GluA2 is coupled to removal of high-conducting Ca2+-permeable AMPA receptors from synapses, resulting in synaptic depression. This work demonstrates a novel mechanism in which mGluR signals release AMPA receptors rapidly from the ER and couple ER release to GluA2 synaptic insertion and GluA1 removal.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, New York, NY, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Pick
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, New York, NY, USA.
authors.forename: Latika
authors.initials: L
authors.lastname: Khatri
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, New York, NY, USA.|Department of Pharmacology and Physiology, Fluminense Federal University, Niteroi, Brazil.
authors.forename: Matheus F
authors.identifier: 0000-0003-3928-0751
authors.initials: MF
authors.lastname: Sathler
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, New York, NY, USA edward.ziff@nyumc.org.
authors.forename: Edward B
authors.identifier: 0000-0001-7389-8649
authors.initials: EB
authors.lastname: Ziff
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate; D019837:Ryanodine Receptor Calcium Release Channel; C000621137:Sec13 protein, rat; C512740:Sec23a protein, rat; D033921:Vesicular Transport Proteins; C104722:glutamate receptor ionotropic, AMPA 2; D002118:Calcium
keywords: COPII; GluA2; calcium permeable AMPA receptor; endoplasmic reticulum; mGluR‐LTD