Synaptic Vesicle Endocytosis Occurs on Multiple Timescales and Is Mediated by Formin-Dependent Actin Assembly
Synaptic Vesicle Endocytosis Occurs on Multiple Timescales and Is Mediated by Formin-Dependent Actin Assembly
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DOI：
10.1016/j.neuron.2017.02.011
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发表时间：
2017-02-22
期刊：
影响因子：
16.2
通讯作者：
Haucke, Volker
中科院分区：
文献类型：
--
作者：
Soykan, Tolga;Kaempf, Natalie;Haucke, Volker
神经传递的基础是突触囊泡（SV）的胞吐融合，随后是胞吞膜的回收和SV的重组。最近的数据表明，在生理温度下，SV通过网格蛋白非依赖性超快内吞作用（UFE）在数百毫秒内内化，而其他研究已经假设SV蛋白的网格蛋白介导的内吞作用（CME）在几秒到几十秒的时间尺度上起关键作用。在这里，我们证明了使用培养的海马神经元作为模型，在生理温度下SV内吞作用发生在几个时间尺度上，从不到一秒到几秒，但在很大程度上是独立的网格蛋白。SV膜的网格蛋白非依赖性内吞作用（CIE）由肌动蛋白成核形成蛋白（如mDia1）介导，这是SV改革形成突触前内体样空泡所必需的。我们的研究结果解决了以前在该领域的差异，并表明SV膜主要是通过CIE检索介导的formin依赖的肌动蛋白组装。
Neurotransmission is based on the exocytic fusion of synaptic vesicles (SVs) followed by endocytic membrane retrieval and the reformation of SVs. Recent data suggest that at physiological temperature SVs are internalized via clathrin-independent ultrafast endocytosis (UFE) within hundreds of milliseconds, while other studies have postulated a key role for clathrin-mediated endocytosis (CME) of SV proteins on a timescale of seconds to tens of seconds. Here we demonstrate using cultured hippocampal neurons as a model that at physiological temperature SV endocytosis occurs on several timescales from less than a second to several seconds, yet, is largely independent of clathrin. Clathrin-independent endocytosis (CIE) of SV membranes is mediated by actin-nucleating formins such as mDia1, which are required for the formation of presynaptic endosome-like vacuoles from which SVs reform. Our results resolve previous discrepancies in the field and suggest that SV membranes are predominantly retrieved via CIE mediated by formin-dependent actin assembly.