Abstract

Cytokinesis is the division of one cell into two genetically identical daughter cells due to the ingression of an actin-myosin based contractile ring. Cytokinesis failure can lead to genomic instability and cancer. In human cells, contractile ring formation and ingression depends on active RhoA, which forms in a discrete region of the cortex during anaphase. Signals from the mitotic spindle shape the zone of active RhoA, but the mechanism is still poorly understood. We investigate how this discrete zone of active RhoA is formed to establish the division plane. Ect2, the guanine nucleotide exchange factor for RhoA, localizes to the anaphase spindle and activates RhoA after anaphase onset. We found that Ect2 is also recruited to the equatorial cortex in a RhoA-dependent manner, suggesting a positive feedback loop reinforces the activation of RhoA in the division plane. Ect2’s cortical interaction is essential for its activity, and one hypothesis is that cortical Ect2 is more active vs. Ect2 in other locations of the cell. Furthermore, Ect2 can interact with anillin, a conserved scaffold protein that also localizes to the cell cortex during anaphase and is essential for cytokinesis. In anillin-depleted cells, the cortical pool of Ect2 is lost, which could lead to decreased localization of active RhoA and unstable furrowing. We hypothesize that in human cells, the Ect2-anillin interaction anchors anaphase spindle microtubules to the equatorial cortex to generate active RhoA in a discrete zone to form the contractile ring and maintain its ingression in the correct plane.