Autophagy controls centrosome number by degrading Cep63.
Autophagy controls centrosome number by degrading Cep63.
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DOI：
10.1038/ncomms13508
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发表时间：
2016-11-21
影响因子：
16.6
通讯作者：
Shimizu S
中科院分区：
文献类型：
--
作者：
Watanabe Y;Honda S;Konishi A;Arakawa S;Murohashi M;Yamaguchi H;Torii S;Tanabe M;Tanaka S;Warabi E;Shimizu S
中心体数目与染色体分离和基因组稳定性有关。泛素-蛋白酶体系统被认为是中心体数目的主要调节因子。然而，在这里，我们表明，自噬也调节中心体的数量。自噬缺陷细胞携带额外的中心体。中心体数目的自噬调节依赖于中心体蛋白63（Cep 63），因为缺乏自噬的细胞含有多个Cep 63点，其在野生型细胞中被自噬吞噬和消化，并且Cep 63的上调增加中心体数目。Cep 63通过与p62相互作用被招募到自噬体中，p62是一种对选择性自噬至关重要的分子。在体内，来自自噬缺陷和p62−/−小鼠的造血细胞也含有多个中心体。这些结果表明，自噬通过降解Cep 63来控制中心体数目。 泛素-蛋白酶体系统被认为是中心体数目的主要调节器。Watanabe等人发现，选择性自噬也通过p62依赖性的中心体蛋白63向自噬体的募集在调节中心体数量中发挥作用。
Centrosome number is associated with the chromosome segregation and genomic stability. The ubiquitin–proteasome system is considered to be the main regulator of centrosome number. However, here we show that autophagy also regulates the number of centrosomes. Autophagy-deficient cells carry extra centrosomes. The autophagic regulation of centrosome number is dependent on a centrosomal protein of 63 (Cep63) given that cells lacking autophagy contain multiple Cep63 dots that are engulfed and digested by autophagy in wild-type cells, and that the upregulation of Cep63 increases centrosome number. Cep63 is recruited to autophagosomes via interaction with p62, a molecule crucial for selective autophagy. In vivo, hematopoietic cells from autophagy-deficient and p62−/− mice also contained multiple centrosomes. These results indicate that autophagy controls centrosome number by degrading Cep63. The ubiquitin-proteasome system is thought to be the primary regulator of centrosome number. Here, Watanabe et al. show that selective autophagy also plays a role in regulating centrosome number via p62-dependent recruitment of centrosomal protein 63 to autophagosomes.