Surface diffusion of astrocytic glutamate transporters shapes synaptic transmission
Surface diffusion of astrocytic glutamate transporters shapes synaptic transmission
复制标题
星形胶质细胞谷氨酸转运体的表面扩散塑造突触传递
DOI：
10.1038/nn.3901
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发表时间：
2015-02-01
影响因子：
25
通讯作者：
Oliet, Stephane H. R.
中科院分区：
文献类型：
--
作者：
Murphy-Royal, Ciaran;Dupuis, Julien P.;Oliet, Stephane H. R.
突触中谷氨酸时间进程的控制对于兴奋性传递至关重要。这一过程主要由星形胶质细胞转运蛋白确保，星形胶质细胞转运蛋白的高表达对于补偿其缓慢的转运周期至关重要。虽然调节转运蛋白胞内运输的分子机制已经确定，表面转运蛋白动力学和突触功能之间的关系仍然没有探索。我们发现GLT-1转运蛋白在大鼠星形胶质细胞上具有高度移动的。GLT-1的表面扩散对神经元和胶质细胞的活动敏感，并且在神经元能突触附近强烈减少，有利于转运蛋白保留。值得注意的是，谷氨酸在突触部位的释放增加了GLT-1的扩散，使转运蛋白远离该隔室。在功能上，通过体外和体内交联损害GLT-1膜扩散减缓了兴奋性突触后电流的动力学，表明突触谷氨酸的时间过程延长。据我们所知，这些数据提供了GLT-1表面扩散在塑造突触传递中的生理作用的第一个证据。
Control of the glutamate time course in the synapse is crucial for excitatory transmission. This process is mainly ensured by astrocytic transporters, high expression of which is essential to compensate for their slow transport cycle. Although molecular mechanisms regulating transporter intracellular trafficking have been identified, the relationship between surface transporter dynamics and synaptic function remains unexplored. We found that GLT-1 transporters were highly mobile on rat astrocytes. Surface diffusion of GLT-1 was sensitive to neuronal and glial activities and was strongly reduced in the vicinity of glutamatergic synapses, favoring transporter retention. Notably, glutamate uncaging at synaptic sites increased GLT-1 diffusion, displacing transporters away from this compartment. Functionally, impairing GLT-1 membrane diffusion through cross-linking in vitro and in vivo slowed the kinetics of excitatory postsynaptic currents, indicative of a prolonged time course of synaptic glutamate. These data provide, to the best of our knowledge, the first evidence for a physiological role of GLT-1 surface diffusion in shaping synaptic transmission.