Chu Chih-Wen, Ossipova Olga, Ioannou Andriani, Sokol Sergei Y
Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Sci Rep. 2016 Apr 11;6:24104. doi: 10.1038/srep24104.
PCP proteins maintain planar polarity in many epithelial tissues and have been implicated in cilia development in vertebrate embryos. In this study we examine Prickle3 (Pk3), a vertebrate homologue of Drosophila Prickle, in Xenopus gastrocoel roof plate (GRP). GRP is a tissue equivalent to the mouse node, in which cilia-generated flow promotes left-right patterning. We show that Pk3 is enriched at the basal body of GRP cells but is recruited by Vangl2 to anterior cell borders. Interference with Pk3 function disrupted the anterior polarization of endogenous Vangl2 and the posterior localization of cilia in GRP cells, demonstrating its role in PCP. Strikingly, in cells with reduced Pk3 activity, cilia growth was inhibited and γ-tubulin and Nedd1 no longer associated with the basal body, suggesting that Pk3 has a novel function in basal body organization. Mechanistically, this function of Pk3 may involve Wilms tumor protein 1-interacting protein (Wtip), which physically associates with and cooperates with Pk3 to regulate ciliogenesis. We propose that, in addition to cell polarity, PCP components control basal body organization and function.
PCP蛋白在许多上皮组织中维持平面极性，并与脊椎动物胚胎中的纤毛发育有关。在本研究中，我们在非洲爪蟾胃腔顶板（GRP）中研究了果蝇Prickle的脊椎动物同源物Prickle3（Pk3）。GRP是一种与小鼠节点等效的组织，其中纤毛产生的流动促进左右模式形成。我们发现Pk3在GRP细胞的基体处富集，但被Vangl2招募到细胞前边界。干扰Pk3功能会破坏内源性Vangl2的前极化以及GRP细胞中纤毛的后定位，证明了其在PCP中的作用。令人惊讶的是，在Pk3活性降低的细胞中，纤毛生长受到抑制，γ-微管蛋白和Nedd1不再与基体相关联，这表明Pk3在基体组织中具有新功能。从机制上讲，Pk3的这种功能可能涉及威尔姆斯瘤蛋白1相互作用蛋白（Wtip），它与Pk3物理结合并协同调节纤毛发生。我们提出，除了细胞极性外，PCP成分还控制基体的组织和功能。
