Rashmi Priya1, Xuan Liang2, Jessica L Teo2, Kinga Duszyc2, Alpha S Yap2, Guillermo A Gomez1. 1. Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane, QLD 4072, Australia rashmi.priya@mpi-bn.mpg.de g.gomez@uq.edu.au. 2. Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane, QLD 4072, Australia.
Abstract
Rho kinases (ROCK1 and ROCK2) function downstream of the small GTPase RhoA to drive actomyosin cytoskeletal remodeling. It has often been believed that ROCK1 and ROCK2 may be functionally redundant, as they share a highly conserved kinase domain. However, in this study, we report differential functional effects for these ROCKs at the epithelial zonula adherens (ZA). Using specific siRNA, we found that ROCK1 depletion disrupted cadherin organization at the ZA, accompanied by loss of F-actin and NMIIA, whereas ROCK2 knockdown had no significant effect. Further, ROCK1, but not ROCK2, was necessary to stabilize GTP-RhoA at the ZA, thereby sustaining junctional tension and inhibiting intraepithelial cell movement. We also found that nonmuscle myosin IIA is a major determinant of ROCK1 cortical stability. Thus, despite sharing the catalytic domain with ROCK2, ROCK1 appears to be the dominant kinase essential for junctional integrity and contractile tension at epithelial ZA.
Rho kinases (ROCK1 and ROCK2) function downstream of the small GTPase RhoA to drive actomyosin cytoskeletal remodeling. It has often been believed that ROCK1 and ROCK2 may be functionally redundant, as they share a highly conserved kinase domain. However, in this study, we report differential functional effects for these ROCKs at the epithelial zonula adherens (ZA). Using specific siRNA, we found that ROCK1 depletion disrupted cadherin organization at the ZA, accompanied by loss of F-actin and NMIIA, whereas ROCK2 knockdown had no significant effect. Further, ROCK1, but not ROCK2, was necessary to stabilize GTP-RhoA at the ZA, thereby sustaining junctional tension and inhibiting intraepithelial cell movement. We also found that nonmuscle myosin IIA is a major determinant of ROCK1 cortical stability. Thus, despite sharing the catalytic domain with ROCK2, ROCK1 appears to be the dominant kinase essential for junctional integrity and contractile tension at epithelial ZA.
Authors: Michael Smutny; Hayley L Cox; Joanne M Leerberg; Eva M Kovacs; Mary Anne Conti; Charles Ferguson; Nicholas A Hamilton; Robert G Parton; Robert S Adelstein; Alpha S Yap Journal: Nat Cell Biol Date: 2010-06-13 Impact factor: 28.824
Authors: Guillermo A Gomez; Robert W McLachlan; Selwin K Wu; Benjamin J Caldwell; Elliott Moussa; Suzie Verma; Michele Bastiani; Rashmi Priya; Robert G Parton; Katharina Gaus; Jan Sap; Alpha S Yap Journal: Mol Biol Cell Date: 2015-01-28 Impact factor: 4.138
Authors: Torey R Arnold; Joseph H Shawky; Rachel E Stephenson; Kayla M Dinshaw; Tomohito Higashi; Farah Huq; Lance A Davidson; Ann L Miller Journal: Elife Date: 2019-01-31 Impact factor: 8.140