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

Fabian BockXinyu DongShensen LiOlga M ViquezEric ShaMatthew TantengcoElizabeth M HennenErin J PlosaAlireza RamezaniKyle L BrownYoung Mi WhangAndrew S TerkerJuan Pablo Arroyo OrnelasDavid G HarrisonAgnes B FogoCord H BrakebuschAmbra PozziRoy Zent
Published in: Science advances (2024)
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 G 2 -M checkpoint stability and prevented premature mitotic entry. The repair defects following injury could be rescued by direct myosin inhibition. Thus, Rac1-dependent control of the actin cytoskeleton integrates with the cell cycle to mediate kidney tubular repair by preventing dysmorphic cells from entering cell division.
Keyphrases
  • cell cycle
  • single cell
  • cell migration
  • cell proliferation
  • cell therapy
  • dna damage
  • oxidative stress
  • protein kinase
  • mesenchymal stem cells
  • stem cells
  • weight gain
  • weight loss
  • room temperature