Dierlam Carter, Anyanwu Livinus, Held Stephanie, Newman Robert H, Iyer Jyoti
Department of Cell Biology and Molecular Genetics, University of Maryland College Park, College Park, MD 20742.
Department of Chemistry and Biochemistry, University of Tulsa, Tulsa, OK 74104.
bioRxiv. 2025 Jul 21:2025.07.21.665896. doi: 10.1101/2025.07.21.665896.
Accurate cytokinesis is essential for maintaining genomic integrity. Although the GTPase dynamin has been well studied for its role in vesicular trafficking, its function during mitosis remains poorly understood. In this study, we uncover a novel role for the dynamin homolog, DYN-1, in regulating mitotic spindle pole assembly and the spatiotemporal localization of the key mitotic kinase Polo-like kinase 1 (PLK-1). Our studies demonstrate that the depletion of DYN-1 leads to enlarged metaphase spindle poles and elevated levels of centrosome-associated PLK-1. Strikingly, PLK-1 fails to re-localize from centrosomes to the midbody during late mitosis in a subset of DYN-1-depleted embryos, correlating with abnormal PLK-1 localization at the midbody and defective midbody formation. Importantly, this phenotype is likely not due to increased total PLK-1 protein levels, as DNM2 (human homolog of DYN-1) depletion in HeLa cells did not alter total Plk1 abundance. Together, our findings identify DYN-1 as a new regulator of PLK-1 localization during mitosis and suggest that failure to remove PLK-1 from centrosomes may underlie cytokinesis defects that are observed upon DYN-1 depletion.
精确的胞质分裂对于维持基因组完整性至关重要。尽管GTP酶发动蛋白在囊泡运输中的作用已得到充分研究，但其在有丝分裂过程中的功能仍知之甚少。在本研究中，我们发现发动蛋白同源物DYN-1在调节有丝分裂纺锤体极组装以及关键有丝分裂激酶Polo样激酶1（PLK-1）的时空定位方面具有新作用。我们的研究表明，DYN-1的缺失会导致中期纺锤体极增大以及中心体相关PLK-1水平升高。引人注目的是，在一部分DYN-1缺失的胚胎中，有丝分裂后期PLK-1未能从中心体重新定位到中体，这与PLK-1在中体的异常定位以及中体形成缺陷相关。重要的是，这种表型可能并非由于PLK-1总蛋白水平增加，因为在HeLa细胞中缺失DYN-1的人类同源物DNM2并未改变Plk1的总丰度。总之，我们的研究结果确定DYN-1是有丝分裂期间PLK-1定位的新调节因子，并表明未能从中心体去除PLK-1可能是DYN-1缺失时观察到的胞质分裂缺陷的基础。
