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  • mGluR long-term depression regulates GluA2 association with COPII vesicles and exit from the endoplasmic reticulum.

mGluR long-term depression regulates GluA2 association with COPII vesicles and exit from the endoplasmic reticulum.

The EMBO journal (2016-11-20)
Joseph E Pick, Latika Khatri, Matheus F Sathler, Edward B Ziff
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Glutamate Receptor 2 Antibody, extracellular, clone 6C4, clone 6C4, Chemicon®, from mouse
Sigma-Aldrich
2-APB, A cell-permeable modulator of Ins(1,4,5)P3-induced Ca2+ release.
Sigma-Aldrich
Xestospongin C, film
Sigma-Aldrich
Dantrolene, Sodium Salt, A cell-permeable blocker of intracellular calcium release from the sarcoplasmic reticulum that acts by binding to the ryanodine receptor.