Rac1 promotes kidney collecting duct repair by mechanically coupling cell morphology to mitotic entry
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Rac1 promotes kidney collecting duct repair by mechanically coupling cell morphology to mitotic entry. / Bock, Fabian; Dong, Xinyu; Li, Shensen; Viquez, Olga M.; Sha, Eric; Tantengco, Matthew; Hennen, Elizabeth M.; Plosa, Erin; Ramezani, Alireza; Brown, Kyle L.; Whang, Young Mi; Terker, Andrew S.; Arroyo, Juan Pablo; Harrison, David G.; Fogo, Agnes; Brakebusch, Cord H.; Pozzi, Ambra; Zent, Roy.
In: Science Advances, Vol. 10, No. 6, eadi7840, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Rac1 promotes kidney collecting duct repair by mechanically coupling cell morphology to mitotic entry
AU - Bock, Fabian
AU - Dong, Xinyu
AU - Li, Shensen
AU - Viquez, Olga M.
AU - Sha, Eric
AU - Tantengco, Matthew
AU - Hennen, Elizabeth M.
AU - Plosa, Erin
AU - Ramezani, Alireza
AU - Brown, Kyle L.
AU - Whang, Young Mi
AU - Terker, Andrew S.
AU - Arroyo, Juan Pablo
AU - Harrison, David G.
AU - Fogo, Agnes
AU - Brakebusch, Cord H.
AU - Pozzi, Ambra
AU - Zent, Roy
N1 - Publisher Copyright: Copyright © 2024 the Authors, some rights reserved.
PY - 2024
Y1 - 2024
N2 - 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 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.
AB - 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 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.
U2 - 10.1126/sciadv.adi7840
DO - 10.1126/sciadv.adi7840
M3 - Journal article
C2 - 38324689
AN - SCOPUS:85184723368
VL - 10
JO - Science advances
JF - Science advances
SN - 2375-2548
IS - 6
M1 - eadi7840
ER -
ID: 385017641