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NSF binds calcium to regulate its interaction with AMPA receptor subunit GluR2
Author(s) -
Hanley Jonathan G.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04455.x
Subject(s) - ampa receptor , protein subunit , microbiology and biotechnology , synaptic plasticity , synaptic vesicle , glutamate receptor , biology , synapse , chemistry , receptor , biochemistry , neuroscience , vesicle , membrane , gene
N ‐ethylmaleimide‐sensitive fusion protein (NSF) is essential for numerous Ca 2+ ‐triggered vesicle trafficking events. It functions as a molecular chaperone to regulate trafficking protein complexes such as the soluble NSF attachment protein (SNAP) receptor complex and the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor (AMPAR)‐protein interacting with C‐kinase (PICK1) complex. AMPAR trafficking is fundamental to processes of synaptic plasticity, which may underlie learning and memory. Changes in synaptic strength brought about by AMPAR trafficking are triggered by a post‐synaptic influx of Ca 2+ , which may have numerous molecular targets including PICK1. NSF binds AMPAR subunit glutamate receptor subunit 2 (GluR2) and functions to maintain receptors at the synapse. In this study, it was showed that NSF is a Ca 2+ ‐binding protein and that GluR2–NSF interactions are inhibited by the presence of 15 μmol/L Ca 2+ . NSF Ca 2+ ‐binding is reciprocally inhibited by the presence of GluR2 C‐terminus. Mutant of NSF that binds Ca 2+ with reduced affinity and binds GluR2 with reduced sensitivity to Ca 2+ was identied. In addition, the interaction of βSNAP with PICK1 is sensitive to Ca 2+ . This study demonstrates that the GluR2‐NSF‐βSNAP‐PICK1 complex is regulated directly by Ca 2+ , allowing for the transduction of Ca 2+ signals into concerted alterations in protein–protein interactions to bring about changes in AMPAR trafficking during synaptic plasticity.