Cby1 promotes Ahi1 recruitment to a ring-shaped domain at the centriole-cilium interface and facilitates proper cilium formation and function.
Cby1 promotes Ahi1 recruitment to a ring-shaped domain at the centriole-cilium interface and facilitates proper cilium formation and function.
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DOI：
10.1091/mbc.e14-02-0735
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发表时间：
2014-10-01
影响因子：
3.3
通讯作者：
Stearns T
中科院分区：
文献类型：
--
作者：
Lee YL;Santé J;Comerci CJ;Cyge B;Menezes LF;Li FQ;Germino GG;Moerner WE;Takemaru K;Stearns T
Cby 1定位于中心粒并拮抗经典Wnt信号传导。Cby 1 −/−小鼠有囊性肾，Cby 1促进初级纤毛形成和纤毛募集Arl 13 b。Cby 1与Ofd 1和Ahi 1一起定位于远端中心粒结构域，并且在Cby 1 −/−细胞中，过渡区的Ahi 1的量减少。中心体和纤毛功能的缺陷与称为纤毛病的表型相关综合征有关。Cby 1是果蝇Chibby蛋白的哺乳动物直向同源物，定位于成熟的中心粒，对小鼠多纤毛气道上皮的纤毛发生很重要，并通过直接调节β-连环蛋白拮抗经典Wnt信号传导。我们报告说，小鼠Cby 1基因的缺失导致囊性肾，一种常见的表型纤毛病变，Cby 1有利于形成初级纤毛和纤毛招聘的Joubert综合征蛋白Arl 13 b。Cby 1在成熟中心粒远端的定位依赖于中心粒蛋白Ofd 1。超分辨率显微镜使用三维SIM和STED显示，Cby 1定位到一个250 nm的环在成熟的中心粒的远端，在靠近Ofd 1和Ahi 1，中心粒和纤毛之间的过渡区的组成部分。在Cby 1 −/−细胞中，中心粒定位的Ahi 1而非Ofd 1的数量减少。这表明Cby 1是Ahi 1有效募集所必需的，为Cby 1 −/−细胞中纤毛发生缺陷提供了可能的分子机制。
Cby1 localizes to centrioles and antagonizes canonical Wnt signaling. Cby1−/− mice have cystic kidneys, and Cby1 facilitates primary cilium formation and ciliary recruitment of Arl13b. Cby1 localizes to a distal centriolar domain with Ofd1 and Ahi1, and the amount of Ahi1 at the transition zone is reduced in Cby1−/− cells. Defects in centrosome and cilium function are associated with phenotypically related syndromes called ciliopathies. Cby1, the mammalian orthologue of the Drosophila Chibby protein, localizes to mature centrioles, is important for ciliogenesis in multiciliated airway epithelia in mice, and antagonizes canonical Wnt signaling via direct regulation of β-catenin. We report that deletion of the mouse Cby1 gene results in cystic kidneys, a phenotype common to ciliopathies, and that Cby1 facilitates the formation of primary cilia and ciliary recruitment of the Joubert syndrome protein Arl13b. Localization of Cby1 to the distal end of mature centrioles depends on the centriole protein Ofd1. Superresolution microscopy using both three-dimensional SIM and STED reveals that Cby1 localizes to an ∼250-nm ring at the distal end of the mature centriole, in close proximity to Ofd1 and Ahi1, a component of the transition zone between centriole and cilium. The amount of centriole-localized Ahi1, but not Ofd1, is reduced in Cby1−/− cells. This suggests that Cby1 is required for efficient recruitment of Ahi1, providing a possible molecular mechanism for the ciliogenesis defect in Cby1−/− cells.