Blachon Stephanie, Gopalakrishnan Jayachandran, Omori Yoshihiro, Polyanovsky Andrey, Church Allen, Nicastro Daniela, Malicki Jarema, Avidor-Reiss Tomer
Department of Biology and Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, Massachusetts 02454, USA.
Genetics. 2008 Dec;180(4):2081-94. doi: 10.1534/genetics.108.095141. Epub 2008 Oct 14.
The centriole is the core structure of centrosome and cilium. Failure to restrict centriole duplication to once per cell cycle has serious consequences and is commonly observed in cancer. Despite its medical importance, the mechanism of centriole formation is poorly understood. Asl was previously reported to be a centrosomal protein essential for centrosome function. Here we identify mecD, a severe loss-of-function allele of the asl gene, and demonstrate that it is required for centriole and cilia formation. Similarly, Cep152, the Asl ortholog in vertebrates, is essential for cilia formation and its function can be partially rescued by the Drosophila Asl. The study of Asl localization suggests that it is closely associated with the centriole wall, but is not part of the centriole structure. By analyzing the biogenesis of centrosomes in cells depleted of Asl, we found that, while pericentriolar material (PCM) function is mildly affected, Asl is essential for daughter centriole formation. The clear absence of several centriolar markers in mecD mutants suggests that Asl is critical early in centriole duplication.
中心粒是中心体和纤毛的核心结构。未能将中心粒复制限制在每个细胞周期一次会产生严重后果,并且在癌症中普遍存在。尽管其具有医学重要性,但中心粒形成的机制仍知之甚少。Asl先前被报道为一种对中心体功能至关重要的中心体蛋白。在这里,我们鉴定出mecD,它是asl基因的一个严重功能丧失等位基因,并证明它是中心粒和纤毛形成所必需的。同样,脊椎动物中Asl的直系同源物Cep152对纤毛形成至关重要,其功能可被果蝇Asl部分挽救。对Asl定位的研究表明,它与中心粒壁密切相关,但不是中心粒结构的一部分。通过分析缺乏Asl的细胞中中心体的生物发生,我们发现,虽然中心粒外周物质(PCM)功能受到轻微影响,但Asl对于子中心粒的形成至关重要。mecD突变体中明显缺乏几种中心粒标记物,这表明Asl在中心粒复制的早期至关重要。