Rapid and differential regulation of AMPA and kainate receptors at hippocampal mossy fibre Synapses by PICK1 and GRIP

被引：172

作者：

Hirbec, H ^{[1
]}

Francis, JC ^{[1
]}

Lauri, SE ^{[1
]}

Braithwaite, SP ^{[1
]}

Coussen, F ^{[1
]}

Mulle, C ^{[1
]}

Dev, KK ^{[1
]}

Couthino, V ^{[1
]}

Meyer, G ^{[1
]}

Isaac, JTR ^{[1
]}

Collingridge, GL ^{[1
]}

Henley, JM ^{[1
]}

机构：

[1] Univ Bristol, Sch Med Sci, Dept Anat, MRC Ctr Synapt Plast, Bristol BS8 1TD, Avon, England

来源：

NEURON | 2003年 / 37卷 / 04期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

D O I：

10.1016/S0896-6273(02)01191-1

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

We identified four PDZ domain-containing proteins, syntenin, PICK1, GRIP, and PSD95, as interactors with the kainate receptor (KAR) subunits GluR5(2b), GluR5(2c), and GluR6. Of these, we show that both GRIP and PICK1 interactions are required to maintain KAR-mediated synaptic function at mossy fiber-CA3 synapses. In addition, PKCalpha can phosphorylate ct-GluR5(2b) at residues S880 and S886, and PKC activity is required to maintain KAR-mediated synaptic responses. We propose that PICK1 targets PKCalpha to phosphorylate KARs, causing their stabilization at the synapse by an interaction with GRIP. Importantly, this mechanism is not involved in the constitutive recycling of AMPA receptors since blockade of PDZ interactions can simultaneously increase AMPAR- and decrease KAR-mediated synaptic transmission at the same population of synapses.

引用

页码：625 / 638

页数：14

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