Cep72 regulates the localization of key centrosomal proteins and proper bipolar spindle formation
Cep72 regulates the localization of key centrosomal proteins and proper bipolar spindle formation
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DOI：
10.1038/emboj.2009.161
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发表时间：
2009-07-22
期刊：
影响因子：
11.4
通讯作者：
Yamamoto, Tadashi
中科院分区：
文献类型：
--
作者：
Oshimori, Naoki;Li, Xue;Yamamoto, Tadashi
中心体的微管成核活性和结构完整性对各种细胞功能至关重要。定位于中心体的中心粒周围基质（PCM）的γ-微管蛋白环复合物（γ TuRCs）是微管成核的主要场所。PCM被认为是由两个同源的大卷曲螺旋蛋白质，pericentrin/kendrin和CG-NAP/AKAP 450，它的稳定Kizuna是必不可少的双极纺锤体的形成。然而，这些蛋白质被募集并组织成具有微管组织活性的适当结构的机制知之甚少。在这里，我们确定了中心体蛋白Cep 72作为Kizuna相互作用蛋白。有趣的是，Cep 72对于CG-NAP和Kizuna的定位至关重要。Cep 72还参与γ TuRC向中心体的募集，并且CG-NAP赋予γ TuRC微管成核活性。在有丝分裂期间，Cep 72介导的微管组织对于将纺锤体微管会聚到中心体是重要的，这是染色体对齐和着丝粒之间的张力产生所需要的。我们的研究结果表明，Cep 72是维持微管组织活动和中心体结构完整性所必需的关键蛋白。The EMBO Journal（2009）28，2066-2076. doi：10.1038/doj.2009.161; 2009年6月18日在线发布
Microtubule-nucleation activity and structural integrity of the centrosome are critical for various cellular functions. The gamma-tubulin ring complexes (gamma TuRCs) localizing to the pericentriolar matrix (PCM) of the centrosome are major sites of microtubule nucleation. The PCM is thought to be created by two cognate large coiled-coil proteins, pericentrin/kendrin and CG-NAP/AKAP450, and its stabilization by Kizuna is essential for bipolar spindle formation. However, the mechanisms by which these proteins are recruited and organized into a proper structure with microtubule-organizing activity are poorly understood. Here we identify a centrosomal protein Cep72 as a Kizuna-interacting protein. Interestingly, Cep72 is essential for the localization of CG-NAP and Kizuna. Cep72 is also involved in gamma TuRC recruitment to the centrosome and CG-NAP confers the microtubule-nucleation activity on the gamma TuRCs. During mitosis, Cep72-mediated microtubule organization is important for converging spindle microtubules to the centrosomes, which is needed for chromosome alignment and tension generation between kinetochores. Our findings show that Cep72 is the key protein essential for maintaining microtubule-organizing activity and structural integrity of the centrosome. The EMBO Journal (2009) 28, 2066-2076. doi: 10.1038/emboj.2009.161; Published online 18 June 2009