Identification of the SNARE complex mediating the exocytosis of NMDA receptors
Identification of the SNARE complex mediating the exocytosis of NMDA receptors
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DOI：
10.1073/pnas.1614042113
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发表时间：
2016-10-25
影响因子：
11.1
通讯作者：
Huganir, Richard L.
中科院分区：
文献类型：
--
作者：
Gu, Yi;Huganir, Richard L.
在中枢神经系统中，NMDA受体介导兴奋性神经传递并在突触可塑性中起重要作用。NMDA受体运输的调节对于脑中的神经功能至关重要。在这里，我们直接可视化的NMDA受体在大鼠海马神经元的全内反射荧光显微镜（TIRFM）的个别胞吐事件。我们发现，NMDA受体的组成性胞吐包括从头胞吐和回收事件，这是由不同的Rab蛋白调节。我们还鉴定了SNAP 25-VAMP 1-突触融合蛋白4复合物介导NMDA受体的组成性胞吐作用。瞬时敲除SNARE复合物的每种成分，干扰NMDA受体向突触外膜和突触膜的表面传递。我们的研究揭示了SNAP 25-VAMP 1-syntaxin 4复合物在介导NMDA受体的组成性胞吐中的突触后功能，表明该SNARE复合物参与兴奋性突触传递。
In the central nervous system, NMDA receptors mediate excitatory neurotransmissions and play important roles in synaptic plasticity. The regulation of NMDA receptor trafficking is critical for neural functions in the brain. Here, we directly visualized individual exocytic events of NMDA receptors in rat hippocampal neurons by total internal reflection fluorescence microscopy (TIRFM). We found that the constitutive exocytosis of NMDA receptors included both de novo exocytic and recycling events, which were regulated by different Rab proteins. We also identified the SNAP25-VAMP1-syntaxin4 complex mediating the constitutive exocytosis of NMDA receptors. Transient knockdown of each component of the SNARE complex interfered with surface delivery of NMDA receptors to both extrasynaptic and synaptic membranes. Our study uncovers the postsynaptic function of the SNAP25-VAMP1-syntaxin4 complex in mediating the constitutive exocytosis of NMDA receptors, suggesting that this SNARE complex is involved in excitatory synaptic transmission.