Mical links semaphorins to F-actin disassembly.
Mical links semaphorins to F-actin disassembly.
复制标题
Mical Link将信号量与F-肌动蛋白拆卸。
作者：
细胞表面存在的指导性信号如何对肌动蛋白细胞骨架产生精确影响，人们对此知之甚少。信号素是这些指导性信号中最大的家族之一，因其对细胞运动、导航、血管生成、免疫学和癌症的影响而被广泛研究。信号素/坍塌素的部分特征是基于它们能够极大地改变神经元突起中肌动蛋白细胞骨架的动态，但尽管在信号素受体及其信号通路的鉴定方面取得了相当大的进展，将它们与细胞骨架元件的精确控制联系起来的分子仍然未知。最近，人们发现Mical家族的一些非常特殊的酶蛋白与丛状蛋白的细胞质部分相关联，丛状蛋白是大型的细胞表面信号素受体，并介导轴突导向、突触发生、树突修剪和其他细胞形态变化。Mical酶进行氧化还原（redox）酶促反应，并且还包含在调节细胞形态的蛋白质中发现的结构域。然而，对于Mical或其氧化还原活性在介导形态变化中的作用一无所知。在此我们报道，Mical将信号素及其丛状蛋白受体与肌动蛋白丝（F - 肌动蛋白）动态的精确控制直接联系起来。我们发现，在体内Mical对于信号素 - 丛状蛋白介导的F - 肌动蛋白重组既是必要的也是充分的。同样，我们纯化了Mical蛋白，发现它直接结合F - 肌动蛋白并解聚单个和成束的肌动蛋白丝。我们还发现，Mical利用其氧化还原活性在体内和体外改变F - 肌动蛋白动态，这表明特定的氧化还原信号事件在肌动蛋白细胞骨架调节中具有此前未知的作用。因此，Mical是一种新型的F - 肌动蛋白解聚因子，它提供了一种分子通道，通过该通道，肌动蛋白重组——包括轴突导航在内的细胞形态变化的一个标志——能够在时空上精确地响应信号素而实现。
How instructive cues present on the cell surface have their precise effects on the actin cytoskeleton is poorly understood. Semaphorins are one of the largest families of these instructive cues and are widely studied for their effects on cell movement, navigation, angiogenesis, immunology and cancer. Semaphorins/collapsins were characterized in part on the basis of their ability to drastically alter actin cytoskeletal dynamics in neuronal processes, but despite considerable progress in the identification of semaphorin receptors and their signalling pathways, the molecules linking them to the precise control of cytoskeletal elements remain unknown. Recently, highly unusual proteins of the Mical family of enzymes have been found to associate with the cytoplasmic portion of plexins, which are large cell-surface semaphorin receptors, and to mediate axon guidance, synaptogenesis, dendritic pruning and other cell morphological changes. Mical enzymes perform reduction–oxidation (redox) enzymatic reactions and also contain domains found in proteins that regulate cell morphology. However, nothing is known of the role of Mical or its redox activity in mediating morphological changes. Here we report that Mical directly links semaphorins and their plexin receptors to the precise control of actin filament (F-actin) dynamics. We found that Mical is both necessary and sufficient for semaphorin–plexin-mediated F-actin reorganization in vivo. Likewise, we purified Mical protein and found that it directly binds F-actin and disassembles both individual and bundled actin filaments. We also found that Mical utilizes its redox activity to alter F-actin dynamics in vivo and in vitro, indicating a previously unknown role for specific redox signalling events in actin cytoskeletal regulation. Mical therefore is a novel F-actin-disassembly factor that provides a molecular conduit through which actin reorganization—a hallmark of cell morphological changes including axon navigation—can be precisely achieved spatiotemporally in response to semaphorins.
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DOI：
10.1083/jcb.121.4.867
发表时间：
1993-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fan J;Mansfield SG;Redmond T;Gordon-Weeks PR;Raper JA
通讯作者：
Raper JA
影响因子：
5.3
作者：
Dent, EW;Barnes, AM;Kalil, K
通讯作者：
Kalil, K
影响因子：
25
作者：
Kirilly, Daniel;Gu, Ying;Yu, Fengwei
通讯作者：
Yu, Fengwei
影响因子：
5.3
作者：
Schmidt, Eric F.;Shim, Sang-Ohk;Strittmatter, Stephen M.
通讯作者：
Strittmatter, Stephen M.
DOI：
10.1073/pnas.0509437102
发表时间：
2005-12-27
影响因子：
11.1
作者：
Tilney, LG;DeRosier, DJ
通讯作者：
DeRosier, DJ