Lee Natalie K, Fok Ka Wai, White Amanda, Wilson Nicole H, O'Leary Conor J, Cox Hayley L, Michael Magdalene, Yap Alpha S, Cooper Helen M
Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Nat Commun. 2016 Mar 31;7:11082. doi: 10.1038/ncomms11082.
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.
在上皮形态发生过程中，为维持组织完整性，黏着连接（AJs）必须抵抗动态组织运动施加的机械应力。连接稳定性取决于肌动蛋白环内的肌动球蛋白收缩性。在此，我们描述了轴突导向受体Neogenin的一种新功能，它是控制连接稳定性的肌动蛋白成核机制的关键组成部分。Neogenin缺失会扰乱AJs并减弱连接张力。Neogenin通过招募波状肌动蛋白调节复合体（WRC）和Arp2/3来促进AJs处的肌动蛋白成核。Neogenin的WIRS结构域与WRC之间的直接相互作用对于WRC在空间上受限地募集到连接处至关重要。因此，我们提供了上皮细胞中功能性WIRS-WRC相互作用的首个实例。我们进一步表明Neogenin调节AJ处钙黏蛋白的循环利用。总之，我们确定Neogenin是AJ的关键组成部分，它在其中影响钙黏蛋白动态变化和连接张力。
