PIKE-mediated PI3-kinase activity is required for AMPA receptor surface expression
PIKE-mediated PI3-kinase activity is required for AMPA receptor surface expression
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DOI：
10.1038/emboj.2011.281
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发表时间：
2011-10-19
期刊：
影响因子：
11.4
通讯作者：
Ye, Keqiang
中科院分区：
文献类型：
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作者：
Chan, Chi Bun;Chen, Yongjun;Ye, Keqiang
Ampar(alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic酸受体)是参与突触可塑性形成的离子通道。然而，可塑性刺激与突触后AMPAR转运的分子机制尚不清楚。在这里，我们证明了PIKE(磷酸肌醇3-激酶增强子)GTP酶通过促进GluA2/GRIP1关联来调节神经元AMPAR的活性。派克-L直接与GluA2和GRIP1相互作用，并在甘氨酸诱导NMDA型受体激活后形成三级复合体。派克-L在甘氨酸诱导的GluA2相关的PI3K激活中也是必不可少的。基因消融神经元上的Pike(-/-)抑制GluA2相关的PI3K激活，从而抑制随后GluA2的表面表达和长时程增强的形成。我们的发现表明，派克-L是控制突触AMPAR插入的关键因素。
AMPAR (alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptor) is an ion channel involved in the formation of synaptic plasticity. However, the molecular mechanism that couples plasticity stimuli to the trafficking of postsynaptic AMPAR remains poorly understood. Here, we show that PIKE (phosphoinositide 3-kinase enhancer) GTPases regulate neuronal AMPAR activity by promoting GluA2/GRIP1 association. PIKE-L directly interacts with both GluA2 and GRIP1 and forms a tertiary complex upon glycine-induced NMDA receptor activation. PIKE-L is also essential for glycine-induced GluA2-associated PI3K activation. Genetic ablation of PIKE (PIKE(-/-)) in neurons suppresses GluA2-associated PI3K activation, therefore inhibiting the subsequent surface expression of GluA2 and the formation of long-term potentiation. Our findings suggest that PIKE-L is a critical factor in controlling synaptic AMPAR insertion.