Dreyer Courtney A, VanderVorst Kacey, Carraway Kermit L
Department of Biochemistry and Molecular Medicine and the UC Davis Comprehensive Cancer Center, UC Davis School of Medicine, Sacramento, CA, United States.
Front Cell Dev Biol. 2022 May 11;10:887100. doi: 10.3389/fcell.2022.887100. eCollection 2022.
The establishment of polarity within tissues and dynamic cellular morphogenetic events are features common to both developing and adult tissues, and breakdown of these programs is associated with diverse human diseases. Wnt/Planar cell polarity (Wnt/PCP) signaling, a branch of non-canonical Wnt signaling, is critical to the establishment and maintenance of polarity in epithelial tissues as well as cell motility events critical to proper embryonic development. In epithelial tissues, Wnt/PCP-mediated planar polarity relies upon the asymmetric distribution of core proteins to establish polarity, but the requirement for this distribution in Wnt/PCP-mediated cell motility remains unclear. However, in both polarized tissues and migratory cells, the Wnt/PCP-specific transmembrane protein Vangl is required and appears to serve as a scaffold upon which the core pathway components as well as positive and negative regulators of Wnt/PCP signaling assemble. The current literature suggests that the multiple interaction domains of Vangl allow for the binding of diverse signaling partners for the establishment of context- and tissue-specific complexes. In this review we discuss the role of Vangl as a master scaffold for Wnt/PCP signaling in epithelial tissue polarity and cellular motility events in developing and adult tissues, and address how these programs are dysregulated in human disease.
组织内极性的建立以及动态细胞形态发生事件是发育中和成体组织共有的特征，而这些程序的破坏与多种人类疾病相关。Wnt/平面细胞极性（Wnt/PCP）信号通路是非经典Wnt信号通路的一个分支，对于上皮组织中极性的建立和维持以及对正常胚胎发育至关重要的细胞运动事件起着关键作用。在上皮组织中，Wnt/PCP介导的平面极性依赖于核心蛋白的不对称分布来建立极性，但这种分布在Wnt/PCP介导的细胞运动中的必要性仍不清楚。然而，在极化组织和迁移细胞中，Wnt/PCP特异性跨膜蛋白Vangl都是必需的，并且似乎充当一种支架，Wnt/PCP信号通路的核心组分以及正负调节因子在其上组装。目前的文献表明，Vangl的多个相互作用结构域允许结合多种信号伴侣，以建立特定背景和组织的复合物。在这篇综述中，我们讨论了Vangl作为Wnt/PCP信号通路的主要支架在上皮组织极性以及发育中和成体组织中的细胞运动事件中的作用，并探讨了这些程序在人类疾病中是如何失调的。
