Rac1 promotes kidney collecting duct repair by mechanically coupling cell morphology to mitotic entry.

ABSTRACT: Prolonged obstruction of the ureter, which leads to injury of the kidney collecting ducts, results in permanent structural damage, while early reversal allows for repair. Cell structure is defined by the actin cytoskeleton, which is dynamically organized by small Rho guanosine triphosphatases (GTPases). In this study, we identified the Rho GTPase, Rac1, as a driver of postobstructive kidney collecting duct repair. After the relief of ureteric obstruction, Rac1 promoted actin cytoskeletal reconstitution, which was required to maintain normal mitotic morphology allowing for successful cell division. Mechanistically, Rac1 restricted excessive actomyosin activity that stabilized the negative mitotic entry kinase Wee1. This mechanism ensured mechanical G₂-M checkpoint stability and p

SUBMITTER: Bock F 

PROVIDER: S-EPMC10849615 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature