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

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.

Physiological stress improves stem cell modeling of dystrophic cardiomyopathy

“…S3 ). Thirty-two proteins previously implicated in muscle membrane repair were found on the aptamer panel ( Bansal et al, 2003 ; Benink and Bement, 2005 ; Cai et al, 2009 ; Demonbreun et al, 2016 ; Griffin et al, 2016 ; Leung et al, 2013 ; Marg et al, 2012 ; Nakamura et al, 2023 ; Roostalu and Strahle, 2012 ; Scheffer et al, 2014 ). Analysis of these membrane repair proteins demonstrated a clear response to equibiaxial strain in DMD compared to control hiPSC-CMs ( Fig.…”

Osteopathic Approach for Keloids and Hypertrophic Scars

“…Rho family guanosine triphosphate (GTP)ases (Rho, Rac, and Cdc42) are important pathways mediating metabolism and cellular function. A disturbed function of this communication pathway is found in non-physiological cicatricial processes; an inadequately managed mechanical stimulus stimulates an increased contraction of the Myos (contractures) [ 16 , 36 ]. Fibroblast ion channel disturbances, particularly for calcium (transient receptor potential TRP), facilitate the transition to the Myo, and increase the production of fibronectin and collagen.…”

“…It is not possible to know exactly and in real-time the behavior of the different components that make up the scar. By not respecting the needs of the skin (dermis and epidermis) when an undetermined intensity (pressure or stretching) is applied by the operator, inflammatory, pro-fibrotic phenomena, increased contracture, and further neurological disorders can be reproduced [ 10 , 13 , 16 , 22 , 23 , 31 , 34 , 36 , 43 , 45 - 47 ]. The elasticity of the skin does not depend on the manual approach, but on the processes that arise from the evolution of a lesion towards scar tissue; the skin will always retain an altered mechanical behavior, compared to the uninjured skin [ 14 , 22 , 23 , 30 , 37 , 43 ].…”