alone, led to increased cell motility and accelerated focal adhesion turnover.Notably, motility of double knockdown podocytes lacked directionality and was accompanied by a significant reduction of Cdc42 activity especially at the cell edge.Mechanistically, the loss of Cdc42 activity in double knockdown podocytes was linked to enhanced degradation of the Cdc42-activating protein ARHGEF7, which was rescued by knockdown of the E3 ubiquitin ligase CBL-b.Furthermore, in double knockdown podocytes, ARHGEF7 was not properly localized in focal adhesions, which was rescued by re-expressing either GIT1 or GIT2.Conclusion: GIT1 and GIT2 cooperatively maintain the ARHGEF7-Cdc42 signaling axis, highlighting a previously unrecognized mechanism regulating Rho GTPase activity and cytoskeletal organization in podocytes.I have no potential conflict of interest to disclose.I did not use generative AI and AI-assisted technologies in the writing process.
San et al. (Wed,) studied this question.