Regulation of growth cone actin dynamics by ADF/cofilin
Regulation of growth cone actin dynamics by ADF/cofilin
复制标题
DOI：
10.1177/002215540305100402
复制
发表时间：
2003-04-01
影响因子：
3.2
通讯作者：
Bamburg, JR
中科院分区：
文献类型：
--
作者：
Gungabissoon, RA;Bamburg, JR
神经系统的发育依赖于神经元寻路，在这个过程中，轴突被特定的细胞外信号引导到它们的靶细胞。神经元响应环境引导信号而长距离延伸的能力是由生长锥（growth cone）实现的，生长锥是在神经元过程末端发现的高度能动的结构。生长锥细胞检测方向线索，并以吸引或排斥的运动做出反应。生长锥的运动依赖于肌动蛋白细胞骨架的快速重组，推测是由肌动蛋白相关蛋白在传入的指导信号的控制下介导的。本文综述了这样一个家庭的蛋白质，ADF/cofilins，正在成为生长锥肌动蛋白动力学的关键监管机构。这些蛋白质对于各种不同细胞类型中的快速肌动蛋白周转是必不可少的。ADF/cofilins在生长锥中与肌动蛋白高度共定位，并且是神经突生长所必需的。ADF/cofilin活性通过LIM激酶和弹弓磷酸酶的可逆磷酸化来调节。LIM激酶是Rho GTP酶Rho、Rac和Cdc 42的下游效应物。越来越多的证据表明，细胞外的指导线索可能会局部改变肌动蛋白的动力学，通过调节活性的LIM激酶和ADF/cofilin磷酸酶通过Rho GTP酶。以这种方式，ADF/cofilins和它们的上游效应器可能是关键的，我们的理解如何指导信息被翻译成生长锥肌动蛋白细胞骨架的物理改变。
Nervous system development is reliant on neuronal pathfinding, the process in which axons are guided to their target cells by specific extracellular cues. The ability of neurons to extend over long distances in response to environmental guidance signals is made possible by the growth cone, a highly motile structure found at the end of neuronal processes. Growth cones detect directional cues and respond with either attractive or repulsive movements. The motility of growth cones is dependent on rapid reorganization of the actin cytoskeleton, presumably mediated by actin-associated proteins under the control of incoming guidance signals. This article reviews how one such family of proteins, the ADF/cofilins, are emerging as key regulators of growth cone actin dynamics. These proteins are essential for rapid actin turnover in a variety of different cell types. ADF/cofilins are heavily co-localized with actin in growth cones and are necessary for neurite outgrowth. ADF/cofilin activities are regulated through reversible phosphorylation by LIM kinases and slingshot phosphatases. LIM kinases are downstream effectors of the Rho GTPases Rho, Rac, and Cdc42. Growing evidence suggests that extracellular guidance cues may locally alter actin dynamics by regulating the activity of LIM kinase and ADF/cofilin phosphatases via the Rho GTPases. In this way, ADF/cofilins and their upstream effectors may be pivotal to our understanding of how guidance information is translated into physical alterations of the growth cone actin cytoskeleton.