Open AccessRac1 promotes kidney collecting duct integrity by limiting actomyosin activity
Author(s) -
Fabian Bock,
Bertha C. Elias,
Xinyu Dong,
Diptiben Parekh,
Glenda Mernaugh,
Olga M. Viquez,
Anjana Hassan,
Venkateswara Rao Amara,
Jiageng Liu,
Kyle L. Brown,
Andrew S. Terker,
Manuel Chiusa,
Leslie Gewin,
Agnes B. Fogo,
Cord Brakebusch,
Ambra Pozzi,
Roy Zent
Publication year - 2021
Publication title -
the journal of cell biology/the journal of cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.414
H-Index - 380
eISSN - 1540-8140
pISSN - 0021-9525
DOI - 10.1083/jcb.202103080
Subject(s) - biology , limiting , microbiology and biotechnology , kidney , duct (anatomy) , rac1 , anatomy , genetics , signal transduction , mechanical engineering , engineering
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.