Broad-minded links cell cycle-related kinase to cilia assembly and hedgehog signal transduction.
Broad-minded links cell cycle-related kinase to cilia assembly and hedgehog signal transduction.
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DOI：
10.1016/j.devcel.2009.12.014
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发表时间：
2010-02-16
影响因子：
11.8
通讯作者：
Eggenschwiler JT
中科院分区：
文献类型：
--
作者：
Ko HW;Norman RX;Tran J;Fuller KP;Fukuda M;Eggenschwiler JT
最近的研究结果表明，哺乳动物的声刺猬 (Shh) 信号转导发生在初级纤毛内，尽管 Shh 信号转导和纤毛发生的细胞生物学机制尚未完全阐明。我们发现，小鼠神经管中高水平的“嘘”反应需要一种未表征的含有 TBC 结构域的蛋白质 Broad-thought (Bromi)。我们发现 Bromi 控制纤毛形态和纤毛内 Gli2 的正确定位。使用斑马鱼模型，我们进一步表明溴是纤毛膜和轴丝之间正确关联所必需的。 Bromi 与细胞周期相关激酶 (CCRK) 发生物理相互作用，CCRK 的衣藻同源物调节鞭毛长度。生化和遗传相互作用数据表明 Bromi 促进 CCRK 稳定性和功能。我们认为 Bromi 和 CCRK 通过协调轴丝和纤毛膜的组装来控制初级纤毛的结构，从而使 Gli 蛋白能够响应 Shh 信号而被正确激活。
Recent findings indicate that mammalian Sonic hedgehog (Shh) signal transduction occurs within primary cilia, although the cell biological mechanisms underlying both Shh signaling and ciliogenesis have not been fully elucidated. We show that an uncharacterized TBC domain-containing protein, Broad-minded (Bromi), is required for high-level Shh responses in the mouse neural tube. We find that Bromi controls ciliary morphology and proper Gli2 localization within the cilium. Using a zebrafish model, we further show that Bromi is required for proper association between the ciliary membrane and axoneme. Bromi physically interacts with cell cycle-related kinase (CCRK), whose Chlamydomonas homolog regulates flagellar length. Biochemical and genetic interaction data indicate that Bromi promotes CCRK stability and function. We propose that Bromi and CCRK control the structure of the primary cilium by coordinating assembly of the axoneme and ciliary membrane, allowing Gli proteins to be properly activated in response to Shh signaling.
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影响因子：
64.8
作者：
Eggenschwiler, JT;Espinoza, E;Anderson, KV
通讯作者：
Anderson, KV
影响因子：
9.2
作者：
Endoh-Yamagami, Setsu;Evangelista, Marie;Peterson, Andrew S.
通讯作者：
Peterson, Andrew S.
DOI：
10.1242/dev.029835
发表时间：
2008-12
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Hoover AN;Wynkoop A;Zeng H;Jia J;Niswander LA;Liu A
通讯作者：
Liu A
影响因子：
3.2
作者：
CHAILLEY, B;BOISVIEUXULRICH, E
通讯作者：
BOISVIEUXULRICH, E
影响因子：
3.3
作者：
Hou, YQ;Pazour, GJ;Witman, GB
通讯作者：
Witman, GB