title: Centralspindlin and α-catenin regulate Rho signalling at the epithelial zonula adherens.
abstract: The biological impact of Rho depends critically on the precise subcellular localization of its active, GTP-loaded form. This can potentially be determined by the balance between molecules that promote nucleotide exchange or GTP hydrolysis. However, how these activities may be coordinated is poorly understood. We now report a molecular pathway that achieves exactly this coordination at the epithelial zonula adherens. We identify an extramitotic activity of the centralspindlin complex, better understood as a cytokinetic regulator, which localizes to the interphase zonula adherens by interacting with the cadherin-associated protein, α-catenin. Centralspindlin recruits the RhoGEF, ECT2, to activate Rho and support junctional integrity through myosin IIA. Centralspindlin also inhibits the junctional localization of p190 B RhoGAP, which can inactivate Rho. Thus, a conserved molecular ensemble that governs Rho activation during cytokinesis is used in interphase cells to control the Rho GTPase cycle at the zonula adherens.
authors: Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Queensland, Australia 4072.
authors: Aparna
authors: A
authors: Ratheesh
authors: Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Queensland, Australia 4072.
authors: Guillermo A
authors: GA
authors: Gomez
authors: Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Queensland, Australia 4072.
authors: Rashmi
authors: R
authors: Priya
authors: Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Queensland, Australia 4072.
authors: Suzie
authors: S
authors: Verma
authors: Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Queensland, Australia 4072.
authors: Eva M
authors: EM
authors: Kovacs
authors: Cell Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands.
authors: Kai
authors: K
authors: Jiang
authors: Gurdon Institute and Department of Physiology, Development and Neuroscience, Cambridge University, Tennis Court Rd, Cambridge CB2 1QN, UK.
authors: Nicholas H
authors: NH
authors: Brown
authors: Cell Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands.
authors: Anna
authors: A
authors: Akhmanova
authors: Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Queensland, Australia 4072.
authors: Samantha J
authors: SJ
authors: Stehbens
authors: Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Queensland, Australia 4072.
authors: Alpha S
authors: AS
authors: Yap
mesh_terms: D022005:Adherens Junctions / Q000502:physiology*; D000818:Animals; D018938:Caco-2 Cells; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D004285:Dogs; D004848:Epithelium / Q000378:metabolism / Q000502:physiology*; D005260:Female; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules; D010750:Phosphoproteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015398:Signal Transduction; D013050:Spectrometry, Fluorescence; D051178:alpha Catenin / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D020690:GTPase-Activating Proteins; D008869:Microtubule-Associated Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D051178:alpha Catenin; C085379:rho GTPase-activating protein; C104434:spindlin