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

Abstract

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.