OSGN-1 is a conserved flavin- containing monooxygenase required to stabilize the intercellular bridge in late cytokinesis

• 成果类型: Article
• 署名作者: Goupil, Eugenie; Lacroix, Lea; Briere, Jonathan; Guga, Sandra; Saba-El-Leila, Marc K.; Melochea, Sylvain; Labbe, Jean-Claude
• 署名单位: Universite de Montreal; Universite de Montreal; Universite de Montreal
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11186
• DOI: 10.1073/pnas.2308570121
• 发表日期: 2024-03-12
• 关键词: protein-structure; i-tasser; rhoa; contractility; genetics

摘要

Cytokinesis is the last step of cell division and is regulated by the small GTPase RhoA. RhoA activity is required for all steps of cytokinesis, including prior to abscission when daughter cells are ultimately physically separated. Like germ cells in all animals, the Caenorhabditis elegans embryonic germline founder cell initiates cytokinesis but does not complete abscission, leaving a stable intercellular bridge between the two daughter cells. Here, we identify and characterize C. elegans OSGN-1 as a cytokinetic regulator that promotes RhoA activity during late cytokinesis. Sequence analyses and biochemical reconstitutions reveal that OSGN-1 is a flavin- containing monooxygenase (MO). Genetic analyses indicate that the MO activity of OSGN-1 is required to maintain active RhoA at the end of cytokinesis in the germline founder cell and to stabilize the intercellular bridge. Deletion of OSGIN1 in human cells results in an increase in binucleation as a result of cytokinetic furrow regression, and this phenotype can be rescued by expressing a catalytically active form of C. elegans OSGN- 1, indicating that OSGN-1 and OSGIN1 are functional orthologs. We propose that OSGN-1 and OSGIN1 are conserved MO enzymes required to maintain RhoA activity at the intercellular bridge during late cytokinesis and thus favor its stability, enabling proper abscission in human cells and bridge stabilization in C. elegans germ cells. Significance Cell division is a fundamental biological process that ends with the physical separation of the two daughter cells, a process termed cytokinesis that must be tightly coordinated. Cells that undergo cytokinesis form a transient structure, termed intercellular bridge, where the machinery required for the final cell separation is assembled. The lack of bridge stability can lead to membrane regression and, ultimately, failure of cell division. Using both the nematode Caenorhabditis elegans and human cells as models, we describe a conserved monooxygenase enzyme that functions to stabilize the intercellular bridge and thus favor the proper completion of cell division.