Rac1 promotes kidney collecting duct integrity by limiting actomyosin activity
Open Access
- 14 October 2021
- journal article
- research article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 220 (11)
- https://doi.org/10.1083/jcb.202103080
Abstract
A polarized collecting duct (CD), formed from the branching ureteric bud (UB), is a prerequisite for an intact kidney. The small Rho GTPase Rac1 is critical for actin cytoskeletal regulation. We investigated the role of Rac1 in the kidney collecting system by selectively deleting it in mice at the initiation of UB development. The mice exhibited only a mild developmental phenotype; however, with aging, the CD developed a disruption of epithelial integrity and function. Despite intact integrin signaling, Rac1-null CD cells had profound adhesion and polarity abnormalities that were independent of the major downstream Rac1 effector, Pak1. These cells did however have a defect in the WAVE2–Arp2/3 actin nucleation and polymerization apparatus, resulting in actomyosin hyperactivity. The epithelial defects were reversible with direct myosin II inhibition. Furthermore, Rac1 controlled lateral membrane height and overall epithelial morphology by maintaining lateral F-actin and restricting actomyosin. Thus, Rac1 promotes CD epithelial integrity and morphology by restricting actomyosin via Arp2/3-dependent cytoskeletal branching.Keywords
Funding Information
- U.S. Department of Veterans Affairs (1I01BX002196, 1I01BX002025, 1I01BX003425)
- National Institutes of Health (R01-DK069921, R01-DK127589, R01-DK119212, R01-DK-108968-01, R01-DK56942, P30-DK114809, 2T32DK007569-32)
- American Society of Nephrology
- American Heart Association
- U.S. Department of Veterans Affairs
- National Institutes of Health (CA68485, DK20593, DK58404, DK59637, EY08126)
- National Institutes of Health (S10-OD021630)
- VUMC
- Vanderbilt-Ingram Cancer Center (P30 CA68485)
- Vanderbilt Digestive Disease Research Center (DK058404)
- National Cancer Institute
- National Institutes of Health (5P30 CA68485-19)
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