The planar cell polarity effector Fuz is essential for targeted membrane trafficking, ciliogenesis and mouse embryonic development.
The planar cell polarity effector Fuz is essential for targeted membrane trafficking, ciliogenesis and mouse embryonic development.
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DOI：
10.1038/ncb1966
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发表时间：
2009-10
影响因子：
21.3
通讯作者：
Finnell, Richard H.
中科院分区：
文献类型：
--
作者：
Gray, Ryan S.;Abitua, Philip B.;Wlodarczyk, Bogdan J.;Szabo-Rogers, Heather L.;Blanchard, Otis;Lee, Insuk;Weiss, Greg S.;Liu, Karen J.;Marcotte, Edward M.;Wallingford, John B.;Finnell, Richard H.
平面细胞极性（PCP）信号通路是胚胎发育所必需的，因为它控制着不同的细胞行为，并且“核心PCP”蛋白，如Dishevelled和Frizzled，已被广泛表征。相比之下，“PCP效应”蛋白，如Intu和Fuz，在很大程度上仍然没有研究。这些蛋白质是PCP信号传导所必需的，但从未在哺乳动物中对其进行过研究，其细胞生物学活性仍然完全未知。我们在这里报告，Fuz突变小鼠显示神经管缺陷，骨骼畸形，刺猬信号缺陷源于破坏纤毛。使用生物信息学和成像的在体粘膜纤毛上皮，我们建立了一个核心的作用Fuz膜贩运，显示Fuz是必不可少的运输货物的基体和顶端的纤毛。Fuz也是分泌细胞中胞吐作用所必需的。最后，我们确定了一种新的，Rab-related小GTdR作为Fuz相互作用的合作伙伴，也是必不可少的纤毛和分泌。这些结果是重要的，因为它们提供了新的见解的机制，发育调控系统，如PCP信号接口与基本的细胞系统，如囊泡贩运机械。
The planar cell polarity (PCP) signaling pathway is essential for embryonic development because it governs diverse cellular behaviors, and the “core PCP” proteins, such as Dishevelled and Frizzled, have been extensively characterized. By contrast, the “PCP effector” proteins, such as Intu and Fuz, remain largely unstudied. These proteins are essential for PCP signaling, but they have never been investigated in a mammal and their cell biological activities remain entirely unknown. We report here that Fuz mutant mice display neural tube defects, skeletal dysmorphologies, and Hedgehog signaling defects stemming from disrupted ciliogenesis. Using bioinformatics and imaging of an in vivo mucociliary epithelium, we establish a central role for Fuz in membrane trafficking, showing that Fuz is essential for trafficking of cargo to basal bodies and to the apical tips of cilia. Fuz is also essential for exocytosis in secretory cells. Finally, we identify a novel, Rab-related small GTPase as a Fuz interaction partner that is also essential for ciliogenesis and secretion. These results are significant because they provide novel insights into the mechanisms by which developmental regulatory systems like PCP signaling interface with fundamental cellular systems such as the vesicle trafficking machinery.
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影响因子：
12.3
作者：
Kim WK;Krumpelman C;Marcotte EM
通讯作者：
Marcotte EM
影响因子：
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作者：
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Knapik, Ela W.
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Arnold, K;Bordoli, L;Schwede, T
通讯作者：
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