Direct regulation of Arp2/3 complex activity and function by the actin binding protein coronin.
Direct regulation of Arp2/3 complex activity and function by the actin binding protein coronin.
复制标题
肌动蛋白结合蛋白 Coronin 直接调节 Arp2/3 复合物的活性和功能。
DOI：
10.1083/jcb.200206113
复制
发表时间：
2002-12-23
影响因子：
7.8
通讯作者：
Goode, Bruce L
中科院分区：
文献类型：
--
作者：
Humphries, Christine L;Balcer, Heath I;D'Agostino, Jessica L;Winsor, Barbara;Drubin, David G;Barnes, Georjana;Andrews, Brenda J;Goode, Bruce L
肌动蛋白相关蛋白2/3(Arp2/3)复合体的激活机制一直是近年来研究的热点。在这里，我们确定了一种新的Arp2/3复合体调控模式，它是由高度保守的肌动蛋白结合蛋白Cortin介导的。酵母菌核黄素(Crn1)与Arp2/3复合体物理结合，在体外抑制Wa和Abp1激活的肌动蛋白成核。这种抑制是在没有预先形成的肌动蛋白细丝的情况下发生的，这表明Crn1可能将Arp2/3复合体的活性限制在细丝的两侧。Crn1的抑制活性位于其盘绕的线圈结构域中。Crn1在体内对肌动蛋白斑块的定位以及Crn1与Arp2/3复合体的结合也需要它的卷曲结构域。遗传学研究为这些相互作用和活动提供了体内证据。CRN1的过表达导致Arp2和Crn1p的生长停滞和重新分布到异常的肌动蛋白环中。这些缺陷通过缺失Crn1卷曲的结构域和Arp2/3复合体的p35亚单位的等位基因arc35-26来抑制。更进一步的体内证据表明，Cortin调节Arp2/3复合体的证据来自于观察到crn1和Arp2突变体显示出等位基因特异性的合成相互作用。这项工作确定了Arp2/3复合体的一种新的调节形式，以及对冠状病毒的一种重要的细胞功能。
Mechanisms for activating the actin-related protein 2/3 (Arp2/3) complex have been the focus of many recent studies. Here, we identify a novel mode of Arp2/3 complex regulation mediated by the highly conserved actin binding protein coronin. Yeast coronin (Crn1) physically associates with the Arp2/3 complex and inhibits WA- and Abp1-activated actin nucleation in vitro. The inhibition occurs specifically in the absence of preformed actin filaments, suggesting that Crn1 may restrict Arp2/3 complex activity to the sides of filaments. The inhibitory activity of Crn1 resides in its coiled coil domain. Localization of Crn1 to actin patches in vivo and association of Crn1 with the Arp2/3 complex also require its coiled coil domain. Genetic studies provide in vivo evidence for these interactions and activities. Overexpression of CRN1 causes growth arrest and redistribution of Arp2 and Crn1p into aberrant actin loops. These defects are suppressed by deletion of the Crn1 coiled coil domain and by arc35-26, an allele of the p35 subunit of the Arp2/3 complex. Further in vivo evidence that coronin regulates the Arp2/3 complex comes from the observation that crn1 and arp2 mutants display an allele-specific synthetic interaction. This work identifies a new form of regulation of the Arp2/3 complex and an important cellular function for coronin.