Alix-mediated assembly of the actomyosin-tight junction polarity complex preserves epithelial polarity and epithelial barrier.
Alix-mediated assembly of the actomyosin-tight junction polarity complex preserves epithelial polarity and epithelial barrier.
复制标题
DOI：
10.1038/ncomms11876
复制
发表时间：
2016-06-23
影响因子：
16.6
通讯作者：
d'Azzo A
中科院分区：
文献类型：
--
作者：
Campos Y;Qiu X;Gomero E;Wakefield R;Horner L;Brutkowski W;Han YG;Solecki D;Frase S;Bongiovanni A;d'Azzo A
上皮细胞极性和上皮屏障的维持依赖于肌动蛋白细胞骨架的空间组织和细胞间连接的正确定位/组装。然而，人们对这些过程是如何调节的知之甚少。在这里，我们揭示了多功能蛋白质阿利克斯在这两个过程中的关键作用。在阿利克斯基因敲除小鼠模型中，我们发现脉络丛和室管膜上皮的明显结构变化，如细胞形状和大小不对称，纤毛错位和异常跳动，微绒毛起泡。这些缺陷最终导致细胞过度挤出、侧脑室扩大和脑积水。从机制上讲，我们发现通过与F-肌动蛋白、Par复合物和ZO-1相互作用，阿利克斯确保了顶端限制性肌动球蛋白紧密连接复合物的形成和维持。我们认为，在这种能力中，阿利克斯在建立顶基极性和维持上皮屏障中发挥作用。 细胞间连接的正确组装是维持上皮极性和屏障功能所必需的。Campos等人在此表明，支架蛋白阿利克斯与F-肌动蛋白、Par复合物和ZO-1相互作用，以确保脉络丛上皮中肌动球蛋白紧密连接复合物的形成和维持。
Maintenance of epithelial cell polarity and epithelial barrier relies on the spatial organization of the actin cytoskeleton and proper positioning/assembly of intercellular junctions. However, how these processes are regulated is poorly understood. Here we reveal a key role for the multifunctional protein Alix in both processes. In a knockout mouse model of Alix, we identified overt structural changes in the epithelium of the choroid plexus and in the ependyma, such as asymmetrical cell shape and size, misplacement and abnormal beating of cilia, blebbing of the microvilli. These defects culminate in excessive cell extrusion, enlargement of the lateral ventricles and hydrocephalus. Mechanistically, we find that by interacting with F-actin, the Par complex and ZO-1, Alix ensures the formation and maintenance of the apically restricted actomyosin–tight junction complex. We propose that in this capacity Alix plays a role in the establishment of apical–basal polarity and in the maintenance of the epithelial barrier. Correct assembly of intercellular junctions is required to maintain epithelial polarity and barrier function. Here Campos et al. show that the scaffold protein Alix interacts with F-actin, the Par complex and ZO-1 to ensure the formation and maintenance of the actomyosin tight junction complex in choroid plexus epithelium.