Scar/WAVE has Rac GTPase-independent functions during cell wound repair

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.

Automated summary

Rho family GTPases play a role in regulating actin dynamics, and WAS family proteins are downstream effectors of Rho family GTPases. In this study, it is shown that the WAS protein Scar/WAVE and Rac GTPase are recruited to cell wounds in the Drosophila repair model and are necessary for the formation and maintenance of the actomyosin ring at the wound periphery. SCAR is recruited earlier than Rac and its recruitment is not affected by a Rac inhibitor. While Rac is important for actin recruitment, SCAR organizes and anchors the actomyosin ring to the plasma membrane.