title: ROCK1 but not ROCK2 contributes to RhoA signaling and NMIIA-mediated contractility at the epithelial zonula adherens.
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.
authors.affiliation: 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.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Priya
authors.affiliation: Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane, QLD 4072, Australia.
authors.forename: Xuan
authors.initials: X
authors.lastname: Liang
authors.affiliation: Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane, QLD 4072, Australia.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Teo
authors.affiliation: Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane, QLD 4072, Australia.
authors.forename: Kinga
authors.initials: K
authors.lastname: Duszyc
authors.affiliation: Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane, QLD 4072, Australia.
authors.forename: Alpha S
authors.initials: AS
authors.lastname: Yap
authors.affiliation: 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.
authors.forename: Guillermo A
authors.initials: GA
authors.lastname: Gomez
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism; D022005:Adherens Junctions / Q000201:enzymology / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D006801:Humans; D061986:MCF-7 Cells; D020409:Molecular Motor Proteins / Q000378:metabolism / Q000502:physiology; D009119:Muscle Contraction / Q000502:physiology; D018995:Myosin Heavy Chains / Q000378:metabolism / Q000502:physiology; D024501:Nonmuscle Myosin Type IIB / Q000378:metabolism; D015398:Signal Transduction; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D015820:Cadherins; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D000205:Actomyosin; C515851:ROCK1 protein, human; C515852:ROCK2 protein, human; D054460:rho-Associated Kinases; D024501:Nonmuscle Myosin Type IIB; D018995:Myosin Heavy Chains; D020742:rhoA GTP-Binding Protein