Adult Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
Cell Division and Aneuploidy Laboratory, Clare Hall Laboratories, Cancer Research UK London Research Institute, London, EN6 3LD, UK.
Nat Commun. 2020 Apr 8;11(1):1746. doi: 10.1038/s41467-020-15359-w.
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.
在哺乳动物细胞系中，内体分选复合物需要运输（ESCRT-III）介导胞质分裂，这是物理上分离子细胞并完成细胞分裂的过程。Cep55 蛋白被认为是胞质分裂的主要调节因子，因为它将 ESCRT-III 募集到胞质分裂体（MB），即胞质分裂的部位。然而，这种机制在哺乳动物中的重要性从未被测试过。在这里，我们表明 Cep55 对于小鼠胚胎发育和成年组织稳态是可有可无的。Cep55 敲除的后代表现出小头畸形，原代神经祖细胞需要 Cep55 和 ESCRT 来存活和胞质分裂。然而，Cep55 在胚胎或成年组织中的细胞分裂是可有可无的。在体外，原代成纤维细胞的分裂不需要 Cep55 和 ESCRT-III 在胞质分裂体中进行，并且不受 ESCRT 耗竭的影响。我们的工作将 Cep55 定义为仅在特定组织背景下的胞质分裂调节剂，并需要重新评估替代的 ESCRT 独立的细胞分裂机制。
