Neogenin recruitment of the WAVE regulatory complex maintains adherens junction stability and tension

Nat Commun. 2016 Mar 31:7:11082. doi: 10.1038/ncomms11082.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Actins / physiology
  • Adherens Junctions / metabolism*
  • Caco-2 Cells
  • Cadherins / analysis
  • Cadherins / genetics
  • Cadherins / metabolism
  • GPI-Linked Proteins / metabolism
  • Gene Knockdown Techniques
  • Humans
  • Membrane Proteins / analysis
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Nerve Tissue Proteins / metabolism
  • Wiskott-Aldrich Syndrome Protein Family / genetics
  • Wiskott-Aldrich Syndrome Protein Family / metabolism*
  • Wiskott-Aldrich Syndrome Protein Family / physiology
  • rac GTP-Binding Proteins / metabolism

Substances

  • Actins
  • Cadherins
  • GPI-Linked Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • RGMA protein, human
  • WASF2 protein, human
  • Wiskott-Aldrich Syndrome Protein Family
  • neogenin
  • rac GTP-Binding Proteins