Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
Biochem Biophys Res Commun. 2010 Jun 11;396(4):887-93. doi: 10.1016/j.bbrc.2010.05.017. Epub 2010 May 10.
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.
纤毛是存在于几乎所有脊椎动物细胞表面的微管细胞器。大多数纤毛作为感觉或分子运输结构发挥作用。纤毛功能障碍与人类发育的几种疾病有关。纤毛的组装由中心粒（或基体）启动，几个中心体蛋白参与这个过程。哺乳动物 LIM 蛋白 Ajuba 是一种研究得很好的中心体蛋白，它调节细胞分裂，但它在纤毛发生中的作用尚不清楚。在这项研究中，我们分离了 Ajuba 的斑马鱼同源物，并表明 Ajuba 定位于生长停滞细胞的纤毛基体。Ajuba 的敲低导致左右器官对称性随机化，并改变了负责左右体轴确定的早期基因的表达。在细胞水平上，我们发现 Ajuba 的功能对于包氏囊衬里细胞中的纤毛发生是必需的；正是这些细胞诱导了确定左右轴所需的不对称流体流动。总之，我们的发现确定了 Ajuba 在调节脊椎动物纤毛发生和左右轴确定中的新作用。
