The LIM protein Ajuba is required for ciliogenesis and left-right axis determination in medaka
The LIM protein Ajuba is required for ciliogenesis and left-right axis determination in medaka
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DOI：
10.1016/j.bbrc.2010.05.017
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发表时间：
2010-06-11
影响因子：
3.1
通讯作者：
Nishina, Hiroshi
中科院分区：
文献类型：
--
作者：
Nagai, Yoko;Asaoka, Yoichi;Nishina, Hiroshi
纤毛是存在于几乎所有脊椎动物细胞表面的基于微管的细胞器。大多数纤毛的功能是感觉或分子运输结构。纤毛功能障碍与人类发育的几种疾病有关。纤毛的组装是由中心粒（或基体）启动的，几种中心体蛋白参与了这一过程。哺乳动物的LIM蛋白Ajuba是一个研究充分的中心体蛋白，调节细胞分裂，但其在纤毛发生中的作用是未知的。在这项研究中，我们分离出的青鳉同源物的筋骨草，并表明筋骨草本地化的纤毛在生长停滞细胞的基体。敲除Ajuba导致随机的左右器官不对称和负责左右体轴决定的早期基因的表达改变。在细胞水平上，我们发现，筋骨草功能是必不可少的细胞内衬Kupffer囊泡的纤毛发生，这是这些细胞诱导所需的左右轴确定的不对称流体流动。总之，我们的研究结果确定了一个新的作用筋骨草在脊椎动物纤毛发生和左右轴的决定的调节。(c)2010年爱思唯尔公司All rights reserved.
Cilia are microtubule-based organelles that are present on the surfaces of almost all vertebrate cells. Most cilia function as sensory or molecular transport structures. Malfunctions of cilia have been implicated in several diseases of human development. The assembly of cilia is initiated by the centriole (or basal body), and several centrosomal proteins are involved in this process. The mammalian LIM protein Ajuba is a well-studied centrosomal protein that regulates cell division but its role in ciliogenesis is unknown. In this study, we isolated the medaka homolog of Ajuba and showed that Ajuba localizes to basal bodies of cilia in growth-arrested cells. Knockdown of Ajuba resulted in randomized left-right organ asymmetries and altered expression of early genes responsible for left-right body axis determination. At the cellular level, we found that Ajuba function was essential for ciliogenesis in the cells lining Kupffer's vesicle; it is these cells that induce the asymmetric fluid flow required for left-right axis determination. Taken together, our findings identify a novel role for Ajuba in the regulation of vertebrate ciliogenesis and left-right axis determination. (c) 2010 Elsevier Inc. All rights reserved.