Department of Biology, Syracuse University, Syracuse, NY, USA.
BioInspired Institute, Syracuse University, Syracuse, NY, USA.
Life Sci Alliance. 2022 Mar 18;5(7). doi: 10.26508/lsa.202201362. Print 2022 Jul.
The last stage of cell division involves two daughter cells remaining interconnected by a cytokinetic bridge that is cleaved during abscission. Conserved between the zebrafish embryo and human cells, we found that the oldest centrosome moves in a Rab11-dependent manner towards the cytokinetic bridge sometimes followed by the youngest. Rab11-endosomes are organized in a Rab11-GTP dependent manner at the mother centriole during pre-abscission, with Rab11 endosomes at the oldest centrosome being more mobile compared with the youngest. The GTPase activity of Rab11 is necessary for the centrosome protein, Pericentrin, to be enriched at the centrosome. Reduction in Pericentrin expression or optogenetic disruption of Rab11-endosome function inhibited both centrosome movement towards the cytokinetic bridge and abscission, resulting in daughter cells prone to being binucleated and/or having supernumerary centrosomes. These studies suggest that Rab11-endosomes contribute to centrosome function during pre-abscission by regulating Pericentrin organization resulting in appropriate centrosome movement towards the cytokinetic bridge and subsequent abscission.
细胞分裂的最后阶段涉及两个子细胞通过胞质分裂桥保持相互连接,该桥在分裂过程中被切割。我们发现,在斑马鱼胚胎和人类细胞之间存在保守性,即最古老的中心体以 Rab11 依赖性的方式向胞质分裂桥移动,有时紧随其后的是最年轻的中心体。在分裂前期,Rab11 内体以 Rab11-GTP 依赖性的方式在母中心粒上组织,最古老的中心体上的 Rab11 内体比最年轻的中心体更具流动性。Rab11 的 GTP 酶活性对于中心体蛋白 Pericentrin 在中心体上的富集是必需的。减少 Pericentrin 的表达或光遗传学破坏 Rab11 内体功能,会抑制中心体向胞质分裂桥的运动和分裂,导致子细胞容易出现双核和/或多余的中心体。这些研究表明,Rab11 内体通过调节 Pericentrin 的组织,在分裂前期有助于中心体的功能,从而导致适当的中心体向胞质分裂桥移动,并随后进行分裂。