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.
Highlights
To maintain tissue integrity during epithelial morphogenesis, adherens junctions (AJs) must resist the mechanical stresses exerted by dynamic tissue movements
We show that Neogenin, a member of the deleted in colorectal cancer (DCC) guidance receptor family[23,24], is an essential junctional component where it promotes actin ring stability by spatially coupling Arp2/3-mediated actin nucleation at the AJ via a direct interaction with the Wave regulatory complex (WRC)
Immunolabelling of polarized Caco-2 monolayers demonstrated that Neogenin co-localizes with Ecad at the AJ (Fig. 1a), suggesting that it may participate in junction assembly or maintenance
Summary
To maintain tissue integrity during epithelial morphogenesis, adherens junctions (AJs) must resist the mechanical stresses exerted by dynamic tissue movements. We describe a novel function for the axon guidance receptor, Neogenin, as a key component of the actin nucleation machinery governing junctional stability. Neogenin promotes actin nucleation at AJs by recruiting the Wave regulatory complex (WRC) and Arp2/3. A primary function of the actin ring is to regulate junctional tension through actomyosin contractility[7,8]. We show that Neogenin, a member of the deleted in colorectal cancer (DCC) guidance receptor family[23,24], is an essential junctional component where it promotes actin ring stability by spatially coupling Arp2/3-mediated actin nucleation at the AJ via a direct interaction with the WRC. We demonstrate that Neogenin is pivotal to the maintenance of junctional stability by regulating Ecad recycling and modulating junctional tension via WRC/Arp2/3-mediated actin nucleation
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