CDK5RAP2 is a pericentriolar protein that functions in centrosomal attachment of the γ-tubulin ring complex
CDK5RAP2 is a pericentriolar protein that functions in centrosomal attachment of the γ-tubulin ring complex
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DOI：
10.1091/mbc.e07-04-0371
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发表时间：
2008-01-01
影响因子：
3.3
通讯作者：
Qi, Robert Z.
中科院分区：
文献类型：
--
作者：
Fong, Ka-Wing;Choi, Yuk-Kwan;Qi, Robert Z.
微管的成核和中心体的组织需要伽马微管蛋白，这是一种存在于大分子复合体中的蛋白质，称为伽马微管蛋白环复合体(Gamma TURC)。我们报道了CDK5RAP2的特征，这是一种新的中心体蛋白，其突变与常染色体隐性遗传性原发性小头畸形有关。在体细胞中，CDK5RAP2在细胞周期的所有阶段定位于中央周围物质。当CDK5RAP2过表达时，CDK5RAP2将包括γ-微管蛋白在内的中心体蛋白的子集组装到中心体上，或者在微管破坏的条件下组装成细胞质中的微管核簇。CDK5RAP2通过在从真菌到哺乳动物的一系列生物中发现的几种相关蛋白质中存在的一个短的保守序列与Gamma Turc相关联。CDK5RAP2的结合是Gamma Turc与中心体连接所必需的，但不是Gamma Turc组装所必需的。干扰CDK5RAP2功能使中心体γ微管蛋白离域，抑制中心体微管成核，从而导致间期微管排列紊乱，形成无星有丝分裂纺锤体。总之，CDK5RAP2是中心体周围的一个结构成分，它在伽马图拉连接中发挥作用，因此在中心体的微管组织功能中发挥作用。我们的研究结果表明，CDK5RAP2突变导致的中心体功能障碍可能是常染色体隐性遗传性原发性小头畸形的原因。
Microtubule nucleation and organization by the centrosome require gamma-tubulin, a protein that exists in a macromolecular complex called the gamma-tubulin ring complex (gamma TuRC). We report characterization of CDK5RAP2, a novel centrosomal protein whose mutations have been linked to autosomal recessive primary microcephaly. In somatic cells, CDK5RAP2 localizes throughout the pericentriolar material in all stages of the cell cycle. When overexpressed, CDK5RAP2 assembled a subset of centrosomal proteins including gamma-tubulin onto the centrosomes or under the microtubule-disrupting conditions into microtubule-nucleating clusters in the cytoplasm. CDK5RAP2 associates with the gamma TuRC via a short conserved sequence present in several related proteins found in a range of organisms from fungi to mammals. The binding of CDK5RAP2 is required for gamma TuRC attachment to the centrosome but not for gamma TuRC assembly. Perturbing CDK5RAP2 function delocalized gamma-tubulin from the centrosomes and inhibited centrosomal microtubule nucleation, thus leading to disorganization of interphase microtubule arrays and formation of anastral mitotic spindles. Together, CDK5RAP2 is a pericentriolar structural component that functions in gamma TuRC attachment and therefore in the microtubule organizing function of the centrosome. Our findings suggest that centrosome malfunction due to the CDK5RAP2 mutations may underlie autosomal recessive primary microcephaly.