Biology subjects

Goupil, E.

Publications and source records attributed to Goupil, E..

3 recordsLinked to original sources

bioRxiv2026

The flavin-containing monooxygenases OSGIN1 and OSGIN2 antagonize each other to favor cytokinesis completion

Cytokinesis is a fundamental process that bisects a mother cell into two distinct daughter cells via an ingressing ring of actomyosin. It initiates after anaphase chromosome separation by the mitotic spindle, which coordinates the activation of the small GTPase RhoA at the cell equator. We previously identified OSGIN1 as a flavin-containing monooxygenase enzyme required for cytokinesis completion via the regulation of RhoA activity. Here we show that the OSGIN1 paralog OSGIN2 is also a flavin-containing monooxygenase implicated in cytokinetic regulation. Cells lacking OSGIN2 have reduced RhoA activity and increased rates of cytokinesis failure, similar to OSGIN1-deleted cells. Strikingly, these phenotypes are suppressed in cells lacking both OSGIN1 and OSGIN2, indicating that the two proteins antagonize each other. Consistent with this, we find that OSGIN1 and OSGIN2 form both homo- and heteromeric complexes in vitro and in cells. Together, our results support a model in which OSGIN1 and OSGIN2 both function as negative regulators of RhoA signaling and that their heteromeric interaction during mitosis antagonizes their activity to favor cytokinesis completion.

cell biology↗

bioRxiv2023

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

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 C. 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 novel cytokinetic regulator that promotes RhoA activity during late cytokinesis. Sequence analyses and biochemical reconstitutions reveal that OSGN-1 is a flavin-containing monooxygenase. Genetic analyses indicate that the monooxygenase 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 novel, conserved monooxygenase enzymes required to maintain RhoA activity at the intercellular bridge during late cytokinesis and thus promote its stability, enabling proper abscission in human cells and bridge stabilization in C. elegans germ cells.

cell biology↗

bioRxiv2017

Anillin proteins stabilize the cytoplasmic bridge between the two primordial germ cells during C. elegans embryogenesis

Stable cytoplasmic bridges arise from failed cytokinesis, the last step of cell division, and are a key feature of syncytial architectures in the germ line of most metazoans. Whereas the C. elegans germ line is syncytial, its formation remains poorly understood. We studied the role of ANI-2, a noncanonical and shorter form of the actomyosin scaffold protein anillin that is expressed specifically during embryogenesis in the germ line precursor blastomere, P4. We found that the P4 blastomere does not complete abscission following cytokinesis, leaving a stable cytoplasmic bridge between the two daughter cells. Interestingly, depletion of ANI-2 results in a regression of the membrane partition between the two cells, indicating that ANI-2 is required to stabilize the cytoplasmic bridge. We identified several contractility regulators that, like ANI-2, localize to the cytoplasmic bridge and are required to stabilize it. Epistatic analysis of these regulators mutual dependencies revealed a pathway in which Rho regulators promote ANI-2 accumulation at the stable cytoplasmic bridge, which in turns promotes the accumulation of the non-muscle myosin II NMY-2 and the midbody component CYK-7 at the bridge, in part by limiting the accumulation of canonical anillin ANI-1. Our results uncover key steps in C. elegans germ line formation and define a set of conserved regulators that ensure the proper stability of the primordial germ cell cytoplasmic bridge during embryonic development.

cell biology↗