Saurya Saroj, Roque Hélio, Novak Zsofia A, Wainman Alan, Aydogan Mustafa G, Volanakis Adam, Sieber Boris, Pinto David Miguel Susano, Raff Jordan W
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Micron Oxford Advanced Bioimaging Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
J Cell Sci. 2016 Jul 1;129(13):2514-25. doi: 10.1242/jcs.186460. Epub 2016 May 20.
Centrioles organise centrosomes and cilia, and these organelles have an important role in many cell processes. In flies, the centriole protein Ana1 is required for the assembly of functional centrosomes and cilia. It has recently been shown that Cep135 (also known as Bld10) initially recruits Ana1 to newly formed centrioles, and that Ana1 then recruits Asl (known as Cep152 in mammals) to promote the conversion of these centrioles into centrosomes. Here, we show that ana1 mutants lack detectable centrosomes in vivo, that Ana1 is irreversibly incorporated into centrioles during their assembly and appears to play a more important role in maintaining Asl at centrioles than in initially recruiting Asl to centrioles. Unexpectedly, we also find that Ana1 promotes centriole elongation in a dose-dependent manner: centrioles are shorter when Ana1 dosage is reduced and are longer when Ana1 is overexpressed. This latter function of Ana1 appears to be distinct from its role in centrosome and cilium function, as a GFP-Ana1 fusion lacking the N-terminal 639 amino acids of the protein can support centrosome assembly and cilium function but cannot promote centriole over-elongation when overexpressed.
中心粒组织中心体和纤毛,并且这些细胞器在许多细胞过程中发挥着重要作用。在果蝇中,中心粒蛋白Ana1是功能性中心体和纤毛组装所必需的。最近的研究表明,Cep135(也称为Bld10)最初将Ana1招募到新形成的中心粒上,然后Ana1招募Asl(在哺乳动物中称为Cep152)以促进这些中心粒转化为中心体。在此,我们表明ana1突变体在体内缺乏可检测到的中心体,Ana1在中心粒组装过程中不可逆地整合到中心粒中,并且在将Asl维持在中心粒上似乎比最初将Asl招募到中心粒上发挥更重要的作用。出乎意料的是,我们还发现Ana1以剂量依赖性方式促进中心粒延长:当Ana1剂量降低时中心粒较短,而当Ana1过表达时中心粒较长。Ana1的后一种功能似乎与其在中心体和纤毛功能中的作用不同,因为缺乏该蛋白N端639个氨基酸的GFP-Ana1融合蛋白可以支持中心体组装和纤毛功能,但过表达时不能促进中心粒过度延长。