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Proteolysis of glutamate receptor‐interacting protein by calpain in rat brain: implications for synaptic plasticity
Author(s) -
Lu Xiaoying,
Wyszynski Michael,
Sheng Morgan,
Baudry Michel
Publication year - 2001
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 - 10.1046/j.1471-4159.2001.00359.x
Subject(s) - calpain , ampa receptor , synaptic plasticity , long term potentiation , long term depression , nmda receptor , glutamate receptor , neuroscience , synaptic fatigue , synaptic scaling , microbiology and biotechnology , biology , chemistry , metaplasticity , receptor , biochemistry , enzyme
Activation of the calcium‐dependent protease calpain has been proposed to be a key step in synaptic plasticity in the hippocampus. However, the exact pathway through which calpain mediates or modulates changes in synaptic function remains to be clarified. Here we report that glutamate receptor‐interacting protein (GRIP) is a substrate of calpain, as calpain‐mediated GRIP degradation was demonstrated using three different approaches: (i) purified calpain I digestion of synaptic membranes, (ii) calcium treatment of frozen–thawed brain sections, and (iii) NMDA‐stimulated organotypic hippocampal slice cultures. More importantly, calpain activation resulted in the disruption of GRIP binding to the GluR2 subunit of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA) receptors. Because GRIP has been proposed to function as an AMPA receptor‐targeting and synaptic‐stabilizing protein, as well as a synaptic‐organizing molecule, calpain‐mediated degradation of GRIP and disruption of AMPA receptor anchoring are likely to play important roles in the structural and functional reorganization accompanying synaptic modifications in long‐term potentiation and long‐term depression.