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

Rapid and differential regulation of AMPA and kainate receptors at hippocampal mossy fibre synapses by PICK1 and GRIP.
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DOI:
10.1016/s0896-6273(02)01191-1
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发表时间:
2003-02-20
期刊:
影响因子:
16.2
通讯作者:
Henley, JM
Henley, JM
中科院分区:
医学1区
文献类型:
--
作者:
Hirbec, H;Francis, JC;Lauri, SE;Braithwaite, SP;Coussen, F;Mulle, C;Dev, KK;Couthino, V;Meyer, G;Isaac, JTR;Collingridge, GL;Henley, JM

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我们鉴定了四种含有 PDZ 结构域的蛋白:syntenin、PICK1、GRIP 和 PSD95,它们与红藻氨酸受体 (KAR) 亚基 GluR52b、GluR52c 和 GluR6 相互作用。其中,我们发现 GRIP 和 PICK1 相互作用都是维持苔藓纤维-CA3 突触处 KAR 介导的突触功能所必需的。此外,PKCα 可以在残基 S880 和 S886 处磷酸化 ct-GluR52b,并且需要 PKC 活性来维持 KAR 介导的突触反应。我们认为 PICK1 靶向 PKCα 来磷酸化 KAR,通过与 GRIP 的相互作用使其在突触处稳定。重要的是,这种机制不参与 AMPA 受体的组成型循环,因为阻断 PDZ 相互作用可以同时增加 AMPAR 介导的突触传递并减少同一突触群中 KAR 介导的突触传递。
We identified four PDZ domain-containing proteins, syntenin, PICK1, GRIP, and PSD95, as interactors with the kainate receptor (KAR) subunits GluR52b, GluR52c, 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, PKCα can phosphorylate ct-GluR52b at residues S880 and S886, and PKC activity is required to maintain KAR-mediated synaptic responses. We propose that PICK1 targets PKCα 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.
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