Prickle3 synergizes with Wtip to regulate basal body organization and cilia growth.
Prickle3 synergizes with Wtip to regulate basal body organization and cilia growth.
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DOI：
10.1038/srep24104
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发表时间：
2016-04-11
影响因子：
4.6
通讯作者：
Sokol SY
中科院分区：
文献类型：
--
作者：
Chu CW;Ossipova O;Ioannou A;Sokol SY
PCP蛋白在许多上皮组织中保持平面极性，并与脊椎动物胚胎的纤毛发育有关。在这项研究中，我们研究了刺3（PK 3），果蝇刺的脊椎动物同源物，在爪蟾胃腔顶板（GRP）。GRP是一种相当于小鼠淋巴结的组织，其中纤毛产生的流动促进了左右模式。我们发现，PK 3是丰富的基体GRP细胞，但被招募的Vangl 2前细胞边界。干扰PK 3功能破坏了内源性Vangl 2的前极化和GRP细胞中纤毛的后定位，证明了其在PCP中的作用。引人注目的是，在Pk 3活性降低的细胞中，纤毛生长受到抑制，γ-微管蛋白和Nedd 1不再与基体结合，表明Pk 3在基体组织中具有新的功能。从机制上讲，Pk 3的这种功能可能涉及Wilms肿瘤蛋白1相互作用蛋白（Wtip），它与Pk 3物理关联并协同调节纤毛发生。我们建议，除了细胞极性，PCP组件控制基体组织和功能。
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.