Retrograde regulation of synaptic vesicle endocytosis and recycling
Retrograde regulation of synaptic vesicle endocytosis and recycling
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DOI：
10.1038/nn1114
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发表时间：
2003-09-01
影响因子：
25
通讯作者：
Smith, SJ
中科院分区：
文献类型：
--
作者：
Micheva, KD;Buchanan, J;Smith, SJ
神经递质的持续释放依赖于突触小泡的循环。到目前为止，人们一直认为囊泡再循环仅受突触前神经元信号的调节，但本文报道的大鼠海马神经元的结果表明，事实并非如此。荧光成像和药理学分析表明，突触后产生的一氧化氮(NO)信号可以调节内吞作用和至少一个较晚的突触小泡循环步骤。该逆行通路涉及依赖NMDAR的突触后NO的产生，NO扩散到突触前部位，以及依赖cGMP的突触前磷脂酰肌醇4，5-二磷酸(PIP2)的增加。这些结果表明，突触小泡再循环的调节可能整合了比以往认识到的更广泛的神经活动信号，包括突触后去极化和即刻和附近突触后活动区的NMDAR的激活。
Sustained release of neurotransmitter depends upon the recycling of synaptic vesicles. Until now, it has been assumed that vesicle recycling is regulated by signals from the presynaptic bouton alone, but results from rat hippocampal neurons reported here indicate that this need not be the case. Fluorescence imaging and pharmacological analysis show that a nitric oxide (NO) signal generated postsynaptically can regulate endocytosis and at least one later step in synaptic vesicle recycling. The proposed retrograde pathway involves an NMDA receptor (NMDAR)-dependent postsynaptic production of NO, diffusion of NO to a presynaptic site, and a cGMP-dependent increase in presynaptic phosphatidylinositol 4,5-biphosphate (PIP2). These results indicate that the regulation of synaptic vesicle recycling may integrate a much broader range of neural activity signals than previously recognized, including postsynaptic depolarization and the activation of NMDARs at both immediate and nearby postsynaptic active zones.