Glutamate stimulates glutamate receptor interacting protein 1 degradation by ubiquitin-proteasome system to regulate surface expression of GluR2.
The glutamate receptor interacting protein 1 (GRIP1) is a scaffolding protein in postsynaptic density (PSD), tethering AMPA receptors to other signaling proteins. Here we report that glutamate stimulation caused a rapid reduction in protein levels of GRIP1, but not that of glutamate receptor (GluR) 1, GluR2 and protein interacting with C kinase 1 (PICK1) in rat primary cortical neuron cultures. Down-regulation of GRIP1 by glutamate was blocked by carbobenzoxyl-leucinyl-leucinyl-leucinal (MG132), a proteasome inhibitor and by expression of K48R-ubiquitin, a dominant negative form of ubiquitin. The GRIP1 reduction was inhibited by MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist, but not by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an AMPA receptor antagonist. EGTA and 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetra acetic acid tetrakis (BAPTA), two Ca2+ chelators, but not nifedipine, an L-type Ca2+ channel blocker, prevented GRIP1 degradation. Furthermore, MG132 prevented glutamate-stimulated reduction in surface amount of GluR2, and knockdown of GRIP1 by RNAi against GRIP1 reduced surface GluR2 in neurons. Our results suggest that glutamate induces GRIP1 degradation by proteasome through an NMDA receptor-Ca2+ pathway and that GRIP1 degradation may play an important role in regulating GluR2 surface expression.
T10 T11 T12 T13 T14 T15 T16 T17 T18 T19 T1 T20 T21 T22 T23 T24 T25 T26 T27 T28 T29 T2 T30 T31 T32 T33 T34 T35 T36 T37 T38 T39 T3 T40 T41 T42 T43 T44 T45 T46 T47 T48 T49 T4 T50 T51 T52 T53 T54 T55 T56 T57 T5 T6 T7 T8 T9
CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-Y GENE-Y GENE-Y CHEMICAL GENE-Y GENE-Y GENE-N GENE-N GENE-N GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y CHEMICAL GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-N GENE-N GENE-N GENE-N GENE-Y CHEMICAL GENE-N GENE-N GENE-N GENE-Y GENE-Y GENE-Y GENE-N GENE-N CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
MG132 MK-801 N-methyl-d-aspartate NMDA 6-cyano-7-nitroquinoxaline-2,3-dione CNQX AMPA EGTA 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetra acetic acid tetrakis BAPTA glutamate Ca2+ nifedipine Ca2+ MG132 glutamate Glutamate glutamate GluR2 GRIP1 GRIP1 AMPA GluR2 GRIP1 AMPA receptors proteasome NMDA receptor GRIP1 GluR2 GRIP1 (GluR) 1 GluR2 NMDA protein interacting with C kinase 1 PICK1 GRIP1 glutamate receptor interacting protein 1 GRIP1 proteasome K48R ubiquitin ubiquitin GRIP1 Ca2+ N-methyl-d-aspartate (NMDA) receptor AMPA receptor L-type Ca2+ channel GRIP1 GluR2 glutamate receptor interacting protein 1 ubiquitin proteasome glutamate glutamate glutamate glutamate carbobenzoxyl-leucinyl-leucinyl-leucinal