Trifaró J-M, Gasman S, Gutiérrez L M
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
Acta Physiol (Oxf). 2008 Feb;192(2):165-72. doi: 10.1111/j.1748-1716.2007.01808.x. Epub 2007 Nov 16.
Chromaffin cell exocytosis is a fascinating interplay between secretory vesicles and cellular components. One of these components is the cytoskeleton and its associated regulatory proteins. Transport of chromaffin secretory granules from their site of biosynthesis towards the active site of exocytosis requires both F-actin fine remodelling as well as microtubule trails. At least two molecular motors, myosins II and V, seem to play a crucial role in the control of F-actin dynamics and vectorial vesicle displacement respectively. Vesicle movement experiences spatial restrictions as they approach the cell cortical region, where the F-actin meshwork constitutes a barrier-limiting vesicle access to the plasmalemma. During secretion, cortical F-actin is locally disrupted providing access of vesicles to release sites on the plasmalemma. Removal of the stimulus restores cortical F-actin. Two pathways (Ca2+-scinderin and PKC-MARCKS) control F-actin changes during the secretory cycle . Furthermore, GTPases such as RhoA, that controls F-actin network integrity, and Cdc42 signalling which induces the formation of local actin filaments at active sites, provide additional evidence on the importance of F-actin as a key element in vesicle transport and in the exocytotic machinery of chromaffin cells.
嗜铬细胞胞吐作用是分泌囊泡与细胞成分之间迷人的相互作用。这些成分之一是细胞骨架及其相关的调节蛋白。嗜铬分泌颗粒从其生物合成部位向胞吐作用的活性部位运输既需要F-肌动蛋白的精细重塑,也需要微管踪迹。至少两种分子马达,肌球蛋白II和V,似乎分别在控制F-肌动蛋白动力学和囊泡的矢量位移中起关键作用。当囊泡接近细胞皮质区域时,其移动会受到空间限制,在该区域F-肌动蛋白网络构成了限制囊泡进入质膜的屏障。在分泌过程中,皮质F-肌动蛋白会局部破坏,使囊泡能够进入质膜上的释放位点。去除刺激后,皮质F-肌动蛋白会恢复。两条途径(Ca2+ - 分裂素和蛋白激酶C - 肌醇蛋白激酶)控制分泌周期中F-肌动蛋白的变化。此外,诸如控制F-肌动蛋白网络完整性的RhoA等小G蛋白,以及在活性位点诱导局部肌动蛋白丝形成的Cdc42信号传导,为F-肌动蛋白作为囊泡运输和嗜铬细胞胞吐机制中的关键元素的重要性提供了额外证据。