Abstract

Cytokinesis, the last step of mitosis, describes the physical separation of a cell into two daughters. In metazoan cells, a contractile ring composed of actin and myosin forms at the division plane and constricts the plasma membrane of the cell. Failure to complete cytokinesis or aberrant cell division can result in changes in fate or cause aneuploidy, both of which are hallmarks of cancer and other pathologies. To ensure that the assembly and constriction of the contractile ring is spatiotemporally coordinated with chromosome segregation, multiple pathways function cooperatively to regulate the localization and function of contractile proteins. These include pathways from the mitotic spindle, which provides cues for ring assembly and positioning. In addition, our lab recently uncovered a novel pathway which senses chromatin to position the ring. The work described here helped to elucidate the molecular mechanisms by which spindle-dependent and -independent pathways work together for cytokinesis, and to find novel targets of the chromatin pathway. Here, we show how the binding of importins, microtubules and RhoA are coordinated to regulate the scaffold protein anillin for cytokinesis. We also show that the NLS of Ect2, the activator of RhoA, is required for cytokinesis. Finally, to identify other contractile proteins regulated the Ran pathway in cytokinesis, a BioID of importin-β1 identified 206 potential new mitotic proximity interactors.