Wu Xin-Sheng, McNeil Benjamin D, Xu Jianhua, Fan Junmei, Xue Lei, Melicoff Ernestina, Adachi Roberto, Bai Li, Wu Ling-Gang
National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.
Department of Pulmonary Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
Nat Neurosci. 2009 Aug;12(8):1003-1010. doi: 10.1038/nn.2355. Epub 2009 Jul 26.
Although endocytosis maintains synaptic transmission, how endocytosis is initiated is unclear. We found that calcium influx initiated all forms of endocytosis at a single nerve terminal in rodents, including clathrin-dependent slow endocytosis, bulk endocytosis, rapid endocytosis and endocytosis overshoot (excess endocytosis), with each being evoked with a correspondingly higher calcium threshold. As calcium influx increased, endocytosis gradually switched from very slow endocytosis to slow endocytosis to bulk endocytosis to rapid endocytosis and to endocytosis overshoot. The calcium-induced endocytosis rate increase was a result of the speeding up of membrane invagination and fission. Pharmacological experiments suggested that the calcium sensor mediating these forms of endocytosis is calmodulin. In addition to its role in recycling vesicles, calcium/calmodulin-initiated endocytosis facilitated vesicle mobilization to the readily releasable pool, probably by clearing fused vesicle membrane at release sites. Our findings provide a unifying mechanism for the initiation of various forms of endocytosis that are critical in maintaining exocytosis.
虽然内吞作用维持着突触传递，但内吞作用是如何启动的尚不清楚。我们发现，在啮齿动物的单个神经末梢，钙内流启动了所有形式的内吞作用，包括网格蛋白依赖性慢内吞作用、批量内吞作用、快速内吞作用和内吞作用过冲（过度内吞作用），每种内吞作用都由相应更高的钙阈值诱发。随着钙内流增加，内吞作用逐渐从非常缓慢的内吞作用转变为慢内吞作用、批量内吞作用、快速内吞作用和内吞作用过冲。钙诱导的内吞作用速率增加是膜内陷和裂变加速的结果。药理学实验表明，介导这些形式内吞作用的钙传感器是钙调蛋白。除了在回收囊泡中的作用外，钙/钙调蛋白启动的内吞作用促进了囊泡向易释放池的移动，可能是通过清除释放位点处融合的囊泡膜来实现的。我们的研究结果为各种形式的内吞作用的启动提供了一种统一机制，这些内吞作用对于维持胞吐作用至关重要。
