Chesarone Melissa, Gould Christopher J, Moseley James B, Goode Bruce L
Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, MA 02454, USA.
Dev Cell. 2009 Feb;16(2):292-302. doi: 10.1016/j.devcel.2008.12.001.
Normal cellular development and function require tight spatiotemporal control of actin assembly. Formins are potent actin assembly factors that protect the growing ends of actin filaments from capping proteins. However, it is unresolved how the duration of formin-mediated actin assembly events is controlled, whether formins are actively displaced from growing ends, and how filament length is regulated in vivo. Here, we identify Bud14 as a high-affinity inhibitor of the yeast formin Bnr1 that rapidly displaces the Bnr1 FH2 domain from growing barbed ends. Consistent with these activities, bud14Delta cells display fewer actin cables, which are aberrantly long, bent, and latrunculinA resistant, leading to defects in secretory vesicle movement. Moreover, bud14Delta suppressed mutations that cause abnormally numerous and shortened cables, restoring wild-type actin architecture. From these results, we propose that formin displacement factors regulate filament length and are required in vivo to maintain proper actin network architecture and function.
正常的细胞发育和功能需要对肌动蛋白组装进行严格的时空控制。formin是强大的肌动蛋白组装因子，可保护肌动蛋白丝的生长末端免受封端蛋白的影响。然而，尚不清楚formin介导的肌动蛋白组装事件的持续时间是如何控制的，formin是否从生长末端被主动取代，以及在体内如何调节丝的长度。在这里，我们鉴定出Bud14是酵母formin Bnr1的高亲和力抑制剂，它能迅速将Bnr1 FH2结构域从生长的带刺末端取代。与这些活性一致，bud14Delta细胞显示出较少的肌动蛋白电缆，这些电缆异常长、弯曲且对LatrunculinA有抗性，导致分泌囊泡运动出现缺陷。此外，bud14Delta抑制了导致异常多且短的电缆的突变，恢复了野生型肌动蛋白结构。从这些结果中，我们提出formin置换因子调节丝的长度，并且在体内是维持适当的肌动蛋白网络结构和功能所必需的。
