Postsynaptic RIM1 modulates synaptic function by facilitating membrane delivery of recycling NMDARs in hippocampal neurons.
Postsynaptic RIM1 modulates synaptic function by facilitating membrane delivery of recycling NMDARs in hippocampal neurons.
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突触后 RIM1 通过促进海马神经元中回收 NMDAR 的膜传递来调节突触功能
DOI：
10.1038/s41467-018-04672-0
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发表时间：
2018-06-11
影响因子：
16.6
通讯作者：
Qiu S
中科院分区：
文献类型：
--
作者：
Wang J;Lv X;Wu Y;Xu T;Jiao M;Yang R;Li X;Chen M;Yan Y;Chen C;Dong W;Yang W;Zhuo M;Chen T;Luo J;Qiu S
NMDA受体（NMDARs）是兴奋性突触传递和突触可塑性的关键。突触NMDAR的数量和亚基组成受到神经元活动和感觉经验的严格控制，但介导NMDAR运输的分子机制仍然知之甚少。在这里，我们报告说，RIM1，在突触前囊泡释放的一个公认的作用，也定位在小鼠海马突触后。海马CA1区的突触后RIM1是基础NMDAR介导的突触反应所必需的，而不是AMPA受体（AMPAR）介导的突触反应，并有助于突触可塑性和海马依赖性记忆。此外，海马神经元中的RIM 1水平影响组成型和调节型NMDAR运输，而不影响组成型AMPAR运输。我们进一步证明，RIM1结合Rab11通过其N末端，RIM1的敲低损害膜插入Rab11阳性回收内体含有NMDAR。总之，这些结果确定了一个RIM1依赖的机制，通过促进膜传递回收NMDAR调节突触功能的关键。
NMDA receptors (NMDARs) are crucial for excitatory synaptic transmission and synaptic plasticity. The number and subunit composition of synaptic NMDARs are tightly controlled by neuronal activity and sensory experience, but the molecular mechanism mediating NMDAR trafficking remains poorly understood. Here, we report that RIM1, with a well-established role in presynaptic vesicle release, also localizes postsynaptically in the mouse hippocampus. Postsynaptic RIM1 in hippocampal CA1 region is required for basal NMDAR-, but not AMPA receptor (AMPAR)-, mediated synaptic responses, and contributes to synaptic plasticity and hippocampus-dependent memory. Moreover, RIM1 levels in hippocampal neurons influence both the constitutive and regulated NMDAR trafficking, without affecting constitutive AMPAR trafficking. We further demonstrate that RIM1 binds to Rab11 via its N terminus, and knockdown of RIM1 impairs membrane insertion of Rab11-positive recycling endosomes containing NMDARs. Together, these results identify a RIM1-dependent mechanism critical for modulating synaptic function by facilitating membrane delivery of recycling NMDARs.
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影响因子：
5.7
作者：
Anggono V;Huganir RL
通讯作者：
Huganir RL
影响因子：
5.5
作者：
Cheng, Jia;Liu, Wenhua;Yan, Zhen
通讯作者：
Yan, Zhen
DOI：
10.1073/pnas.1614042113
发表时间：
2016-10-25
影响因子：
11.1
作者：
Gu, Yi;Huganir, Richard L.
通讯作者：
Huganir, Richard L.
影响因子：
16.2
作者：
Han Y;Kaeser PS;Südhof TC;Schneggenburger R
通讯作者：
Schneggenburger R
影响因子：
16.2
作者：
Betz, A;Thakur, P;Brose, N
通讯作者：
Brose, N