Postsynaptic δ1 glutamate receptor assembles and maintains hippocampal synapses via Cbln2 and neurexin
Postsynaptic δ1 glutamate receptor assembles and maintains hippocampal synapses via Cbln2 and neurexin
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DOI：
10.1073/pnas.1802737115
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发表时间：
2018-06-05
影响因子：
11.1
通讯作者：
Nicoll, Roger A.
中科院分区：
文献类型：
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作者：
Tao, Wucheng;Diaz-Alonso, Javier;Nicoll, Roger A.
谷氨酸受体（GluD1）是几十年前克隆的，在大脑的许多区域广泛表达。然而，它在这些脑回路中的功能作用仍不清楚。在这里，我们发现GluD1是海马兴奋性突触形成和维持所必需的。GluD1的作用在Cbln2敲除小鼠中缺失。此外，GluD1的作用需要突触前神经蛋白1 β携带剪接位点4插入物（+S4）的存在。总之，我们的研究结果表明，海马突触的组装和维持需要一个三方分子复合物，其中配体Cbln2与突触前神经素1 β (+S4)和突触后GluD1结合。我们提供的证据表明，这种机制可能适用于其他广泛表达GluD1的前脑突触。
The delta 1 glutamate receptor (GluD1) was cloned decades ago and is widely expressed in many regions of the brain. However, its functional roles in these brain circuits remain unclear. Here, we find that GluD1 is required for both excitatory synapse formation and maintenance in the hippocampus. The action of GluD1 is absent in the Cbln2 knockout mouse. Furthermore, the GluD1 actions require the presence of presynaptic neurexin 1 beta carrying the splice site 4 insert (+S4). Together, our findings demonstrate that hippocampal synapse assembly and maintenance require a tripartite molecular complex in which the ligand Cbln2 binds with presynaptic neurexin 1 beta (+S4) and postsynaptic GluD1. We provide evidence that this mechanism may apply to other forebrain synapses, where GluD1 is widely expressed.