title: Neogenin recruitment of the WAVE regulatory complex maintains adherens junction stability and tension.
abstract: To maintain tissue integrity during epithelial morphogenesis, adherens junctions (AJs) must resist the mechanical stresses exerted by dynamic tissue movements. Junctional stability is dependent on actomyosin contractility within the actin ring. Here we describe a novel function for the axon guidance receptor, Neogenin, as a key component of the actin nucleation machinery governing junctional stability. Loss of Neogenin perturbs AJs and attenuates junctional tension. Neogenin promotes actin nucleation at AJs by recruiting the Wave regulatory complex (WRC) and Arp2/3. A direct interaction between the Neogenin WIRS domain and the WRC is crucial for the spatially restricted recruitment of the WRC to the junction. Thus, we provide the first example of a functional WIRS-WRC interaction in epithelia. We further show that Neogenin regulates cadherin recycling at the AJ. In summary, we identify Neogenin as a pivotal component of the AJ, where it influences both cadherin dynamics and junctional tension.
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Natalie K
authors.initials: NK
authors.lastname: Lee
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Ka Wai
authors.initials: KW
authors.lastname: Fok
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Amanda
authors.initials: A
authors.lastname: White
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Nicole H
authors.initials: NH
authors.lastname: Wilson
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Conor J
authors.initials: CJ
authors.lastname: O'Leary
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Hayley L
authors.initials: HL
authors.lastname: Cox
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Magdalene
authors.initials: M
authors.lastname: Michael
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Alpha S
authors.initials: AS
authors.lastname: Yap
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Cooper
mesh_terms: D000199:Actins / Q000378:metabolism / Q000502:physiology; D022005:Adherens Junctions / Q000378:metabolism*; D018938:Caco-2 Cells; D015820:Cadherins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D020744:rac GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000199:Actins; D015820:Cadherins; D058851:GPI-Linked Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C522183:RGMA protein, human; C120152:WASF2 protein, human; D051300:Wiskott-Aldrich Syndrome Protein Family; C091279:neogenin; D020744:rac GTP-Binding Proteins