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Cordon bleu promotes the assembly of brush border microvilli

机译:蓝带促进刷缘微绒毛的组装

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摘要

Microvilli are actin-based protrusions found on the surface of diverse cell types, where they amplify membrane area and mediate interactions with the external environment. In the intestinal tract, these protrusions play central roles in nutrient absorption and host defense and are therefore essential for maintaining homeostasis. However, the mechanisms controlling microvillar assembly remain poorly understood. Here we report that the multifunctional actin regulator cordon bleu (COBL) promotes the growth of brush border (BB) microvilli. COBL localizes to the base of BB microvilli via a mechanism that requires its proline-rich N-terminus. Knockdown and overexpression studies show that COBL is needed for BB assembly and sufficient to induce microvillar growth using a mechanism that requires functional WH2 domains. We also find that COBL acts downstream of the F-BAR protein syndapin-2, which drives COBL targeting to the apical domain. These results provide insight into a mechanism that regulates microvillar growth during epithelial differentiation and have significant implications for understanding the maintenance of intestinal homeostasis.
机译:微绒毛是基于肌动蛋白的突起物,存在于多种细胞类型的表面上,它们在其中放大膜区域并介导与外部环境的相互作用。在肠道中,这些突起在营养吸收和宿主防御中起着核心作用,因此对于维持体内稳态至关重要。但是,控制微绒毛组装的机制仍然知之甚少。在这里我们报告多功能肌动蛋白调节剂蓝带(COBL)促进刷缘(BB)微绒毛的增长。 COBL通过需要富含脯氨酸的N端的机制定位在BB微绒毛的底部。抑制和过度表达研究表明,BB组装需要COBL,并且需要使用需要WH2功能域的机制才能诱导微绒毛生长。我们还发现,COBL作用于F-BAR蛋白syndapin-2的下游,该蛋白驱动COBL靶向顶端结构域。这些结果提供了一种在上皮分化过程中调节微绒毛生长的机制的见解,并且对理解肠道稳态的维持具有重要意义。

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