PICK1 Mediates Synaptic Recruitment of AMPA Receptors at Neurexin-Induced Postsynaptic Sites
PICK1 Mediates Synaptic Recruitment of AMPA Receptors at Neurexin-Induced Postsynaptic Sites
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DOI：
10.1523/jneurosci.0296-14.2014
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发表时间：
2014-11
期刊：
影响因子：
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通讯作者：
Junyu Xu;C. Kam;Jian‐hong Luo;Jun Xia
中科院分区：
文献类型：
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作者：
Junyu Xu;C. Kam;Jian‐hong Luo;Jun Xia
在中枢神经系统中，突触的形成和成熟在神经元回路的构建和巩固中起着至关重要的作用。Neurexin和neuroligin定位于突触膜两侧，相互作用促进突触的组装和特化。然而，由neurexin-neuroligin复合物诱导的兴奋性突触最初是缺乏AMPA受体的未成熟突触。以前，PICK 1（与C激酶1相互作用的蛋白质）被证明可以聚集并调节AMPA受体的突触定位。在这里，我们报告说，在neurexin诱导的大鼠海马培养神经元的突触发生，PICK 1招募AMPA受体未成熟的突触后位点。AMPA受体的这种突触募集依赖于GluA 2和PICK 1之间的相互作用，以及PICK 1的脂质结合能力，但不依赖于PICK 1和神经配素之间的相互作用。最后，我们的研究结果表明，招募的GluA 2突触可以阻止ICA 69（胰岛细胞自身抗原69 kDa），一个关键的结合伙伴PICK 1。我们的研究表明，PICK 1受ICA 69负调控，可促进突触成熟。
In the CNS, synapse formation and maturation play crucial roles in the construction and consolidation of neuronal circuits. Neurexin and neuroligin localize on the opposite sides of synaptic membrane and interact with each other to promote the assembly and specialization of synapses. However, the excitatory synapses induced by the neurexin–neuroligin complex are initially immature synapses that lack AMPA receptors. Previously, PICK1 (protein interacting with C kinase 1) was shown to cluster and regulate the synaptic localization of AMPA receptors. Here, we report that during synaptogenesis induced by neurexin in cultured neurons from rat hippocampus, PICK1 recruited AMPA receptors to immature postsynaptic sites. This synaptic recruitment of AMPA receptors depended on the interaction between GluA2 and PICK1, and on the lipid-binding ability of PICK1, but not the interaction between PICK1 and neuroligin. Last, our results demonstrated that the recruitment of GluA2 to synapses could be prevented by ICA69 (islet cell autoantigen 69 kDa), a key binding partner of PICK1. Our study showed that PICK1, being negatively regulated by ICA69, could facilitate synapse maturation.