Cep55 promotes cytokinesis of neural progenitors but is dispensable for most mammalian cell divisions
Cep55 promotes cytokinesis of neural progenitors but is dispensable for most mammalian cell divisions
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DOI：
10.1038/s41467-020-15359-w
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发表时间：
2020-04-08
影响因子：
16.6
通讯作者：
Petronczki, Mark
中科院分区：
文献类型：
--
作者：
Tedeschi, Antonio;Almagro, Jorge;Petronczki, Mark
在哺乳动物细胞系中，运输所需的内体分选复合物 (ESCRT)-III 介导脱落，即物理分离子细胞并完成细胞分裂的过程。 Cep55 蛋白被认为是脱落的主要调节因子，因为它将 ESCRT-III 招募到中体 (MB)，即脱落部位。然而，这种机制在哺乳动物生物体中的重要性从未得到测试。在这里，我们证明 Cep55 对于小鼠胚胎发育和成体组织稳态是不可或缺的。 Cep55 敲除后代表现出小头畸形，原代神经祖细胞需要 Cep55 和 ESCRT 才能生存和脱落。然而，Cep55 对于胚胎或成体组织中的细胞分裂来说是可有可无的。在体外，原代成纤维细胞的分裂发生在中间体没有 Cep55 和 ESCRT-III 的情况下，并且不受 ESCRT 耗尽的影响。我们的工作将 Cep55 定义为仅在特定组织环境中的分离调节因子，并且需要重新评估替代的 ESCRT 独立细胞分裂机制。在哺乳动物细胞系中，Cep55 蛋白招募运输所需的内体分选复合物 (ESCRT) 并促进细胞分裂的完成。在这里，作者表明 Cep55 敲除小鼠是可行的，并且体外培养的原代成纤维细胞以不依赖 Cep55 和 ESCRT 的方式分裂。
In mammalian cell lines, the endosomal sorting complex required for transport (ESCRT)-III mediates abscission, the process that physically separates daughter cells and completes cell division. Cep55 protein is regarded as the master regulator of abscission, because it recruits ESCRT-III to the midbody (MB), the site of abscission. However, the importance of this mechanism in a mammalian organism has never been tested. Here we show that Cep55 is dispensable for mouse embryonic development and adult tissue homeostasis. Cep55-knockout offspring show microcephaly and primary neural progenitors require Cep55 and ESCRT for survival and abscission. However, Cep55 is dispensable for cell division in embryonic or adult tissues. In vitro, division of primary fibroblasts occurs without Cep55 and ESCRT-III at the midbody and is not affected by ESCRT depletion. Our work defines Cep55 as an abscission regulator only in specific tissue contexts and necessitates the re-evaluation of an alternative ESCRT-independent cell division mechanism. In mammalian cell lines, Cep55 protein recruits the endosomal sorting complex required for transport (ESCRT) and promotes the completion of cell division. Here, the authors show that Cep55-knockout mice are viable and primary fibroblasts cultured in vitro divide in a Cep55 and ESCRT-independent way.