PDF(Pubmed)
Abstract：
Rho family GTPases regulate both linear and branched actin dynamics by activating downstream effectors to facilitate the assembly and function of complex cellular structures such as lamellipodia and contractile actomyosin rings. Wiskott-Aldrich Syndrome (WAS) family proteins are downstream effectors of Rho family GTPases that usually function in a one-to-one correspondence to regulate branched actin nucleation. In particular, the WAS protein Scar/WAVE has been shown to exhibit one-to-one correspondence with Rac GTPase. Here we show that Rac and SCAR are recruited to cell wounds in the Drosophila repair model and are required for the proper formation and maintenance of the dynamic actomyosin ring formed at the wound periphery. Interestingly, we find that SCAR is recruited to wounds earlier than Rac and is still recruited to the wound periphery in the presence of a potent Rac inhibitor. We also show that while Rac is important for actin recruitment to the actomyosin ring, SCAR serves to organize the actomyosin ring and facilitate its anchoring to the overlying plasma membrane. These differing spatiotemporal recruitment patterns and wound repair phenotypes highlight the Rac-independent functions of SCAR and provide an exciting new context in which to investigate these newly uncovered SCAR functions.
摘要：
Rho家族GTP酶通过激活下游效应子调节线性和分支肌动蛋白动力学，以促进复杂细胞结构的组装和功能，例如层状足和收缩性肌动球蛋白环。Wiskott-Aldrich综合征（WAS）家族蛋白是Rho家族GTP酶的下游效应子，通常以一对一的对应关系发挥作用以调节分支肌动蛋白成核。特别是,WAS蛋白疤痕/波显示与RacGTPase一一对应。在这里，我们表明Rac和SCAR被募集到果蝇修复模型中的细胞伤口中，并且是正确形成和维持伤口周围形成的动态肌动球蛋白环所必需的。有趣的是,我们发现SCAR比Rac更早被招募到伤口,并且在存在有效Rac抑制剂的情况下仍被招募到伤口周围.我们还表明，虽然Rac对于肌动蛋白向肌动球蛋白环的募集很重要，SCAR用于组织肌动球蛋白环并促进其锚定到上覆的质膜。这些不同的时空募集模式和伤口修复表型突出了SCAR的Rac独立功能，并提供了一个令人兴奋的新环境来研究这些新发现的SCAR功能。
