Activity-driven relaxation of the cortical actomyosin II network synchronizes Munc18-1-dependent neurosecretory vesicle docking
Activity-driven relaxation of the cortical actomyosin II network synchronizes Munc18-1-dependent neurosecretory vesicle docking
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DOI：
10.1038/ncomms7297
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发表时间：
2015-02-01
影响因子：
16.6
通讯作者：
Meunier, Frederic A.
中科院分区：
文献类型：
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作者：
Papadopulos, Andreas;Gomez, Guillermo A.;Meunier, Frederic A.
在神经分泌细胞中，分泌小泡(SVS)依赖于钙离子与质膜融合以释放神经递质。SVS如何穿过皮质肌动蛋白网络的致密网状结构到达质膜仍不清楚。在这里，我们揭示了在牛嗜铬细胞中，嵌入在皮质肌动蛋白网络中的SVS在分泌剂的响应下经历了高度同步的向质膜和Munc18-1依赖的对接的转变。这一运动与皮质肌动蛋白网络向同一方向移位相吻合。这两种作用都被肌球蛋白II的基因敲除或药物抑制所消除，这表明肌球蛋白产生的力量在整个细胞皮质中发生了变化。事实上，我们报告了对肌球蛋白II抑制敏感的促分泌剂刺激引起的皮质肌动蛋白网络张力的降低。我们发现，皮质肌动蛋白网络作为一张经历活动依赖性松弛的‘铸网’，从而驱动拴系的SVS朝向质膜，在那里它们经历了Munc18-1依赖的对接。
In neurosecretory cells, secretory vesicles (SVs) undergo Ca2(+)-dependent fusion with the plasma membrane to release neurotransmitters. How SVs cross the dense mesh of the cortical actin network to reach the plasma membrane remains unclear. Here we reveal that, in bovine chromaffin cells, SVs embedded in the cortical actin network undergo a highly synchronized transition towards the plasma membrane and Munc18-1-dependent docking in response to secretagogues. This movement coincides with a translocation of the cortical actin network in the same direction. Both effects are abolished by the knockdown or the pharmacological inhibition of myosin II, suggesting changes in actomyosin-generated forces across the cell cortex. Indeed, we report a reduction in cortical actin network tension elicited on secretagogue stimulation that is sensitive to myosin II inhibition. We reveal that the cortical actin network acts as a 'casting net' that undergoes activity-dependent relaxation, thereby driving tethered SVs towards the plasma membrane where they undergo Munc18-1-dependent docking.