Abstract
GTPases have two interconvertible forms, an active GTP bound form and an inactive GDP bound form. The active GTP bound form binds to downstream effector proteins to transmit cellular signals. Exchange of GDP for GTP is catalyzed by interaction of GTPases with guanine nucleotide exchange factors (GEFs). GTPase activating proteins (GAPs) accelerate GTP hydrolysis of GTPases, to promote the GDP-bound inactive form. Recently, we reported that the GEF called PIX is required for assembly or stability of integrin adhesion complexes (IAC) in striated muscle. However, a GAP for the PIX pathway has yet to be identified in any cell type or organism. In this study, we show that RRC-1 is a GAP protein for the PIX-1 pathway in striated muscle. From a screen in C. elegans of mutants in 18 proteins containing Rho GAP domains and expressed in muscle, we found that loss of function of rrc-1 results in the same phenotype as loss of function of the GEF, pix-1. Mutations in either gene result in loss of IAC accumulation at the muscle cell boundaries (MCB) but not at M-lines and dense bodies, and reduced whole animal locomotion. Both RRC-1 and PIX-1 localize to IACs at MCBs, M-lines, and dense bodies, and have been shown to affect Rac GTPase activity. RNAi knockdown of GIT-1, a known scaffold for PIX-1, results in a reduction in the level of RRC-1 protein. Overexpression of PIX-1 suppresses the rrc-1 MCB defect. rrc-1, pix-1, and git-1 show genetic interactions.
Competing Interest Statement
The authors have declared no competing interest.