Apical constriction is critical for epithelial morphogenesis, including neural tube formation. Vertebrate apical constriction is induced by di‐phosphorylated myosin light chain (ppMLC)‐driven contraction of actomyosin‐based circumferential rings (CRs), also known as perijunctional actomyosin rings, around apical junctional complexes (AJCs), mainly consisting of tight junctions (TJs) and adherens junctions (AJs). Here, we revealed a ppMLC‐triggered system at TJ‐associated CRs for vertebrate apical constriction involving microtubules, LUZP1, and myosin phosphatase. We first identified LUZP1 via unbiased screening of microtubule‐associated proteins in the AJC‐enriched fraction. In cultured epithelial cells, LUZP1 was found localized at TJ‐, but not at AJ‐, associated CRs, and LUZP1 knockout resulted in apical constriction defects with a significant reduction in ppMLC levels within CRs. A series of assays revealed that ppMLC promotes the recruitment of LUZP1 to TJ‐associated CRs, where LUZP1 spatiotemporally inhibits myosin phosphatase in a microtubule‐facilitated manner. Our results uncovered a hitherto unknown microtubule‐LUZP1 association at TJ‐associated CRs that inhibits myosin phosphatase, contributing significantly to the understanding of vertebrate apical constriction.

中文翻译：

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紧密连接周围的微管LUZP1缔合促进上皮细胞根尖收缩

根尖收缩对于上皮形态发生（包括神经管形成）至关重要。椎体根尖收缩是由二磷酸肌球蛋白轻链（ppMLC）驱动的基于肌动蛋白的圆周环（CR）收缩，也称为结节周围的肌动蛋白环引起的，它围绕根尖连接复合体（AJC）周围，主要由紧密连接（TJs）组成）和粘附连接（AJ）。在这里，我们揭示了TJ相关CR处的ppMLC触发系统，用于涉及微管，LUZP1和肌球蛋白磷酸酶的脊椎动物根尖收缩。我们首先通过对AJC富集级分中微管相关蛋白的无偏筛选来鉴定LUZP1。在培养的上皮细胞中，发现LUZP1位于相关的CR的TJ-而非AJ-，LUZP1基因敲除导致根尖收缩缺陷，CRs中的ppMLC水平显着降低。一系列分析表明，ppMLC促进LUZP1向TJ相关CR募集，其中LUZP1时空以微管促成方式抑制肌球蛋白磷酸酶。我们的研究结果揭示了迄今为止未知的TJ相关CRs的微管LUZP1协会，该协会抑制肌球蛋白磷酸酶，大大有助于了解脊椎动物的心尖收缩。