KIF2A stabilizes intercellular bridge microtubules to maintain mouse embryonic stem cell cytokinesis.

Abstract

Cytokinesis, the final stage of cell division, serves to physically separate daughter cells. In cultured naïve mouse embryonic stem cells, cytokinesis lasts unusually long. Here, we describe a novel function for the kinesin-13 member KIF2A in this process. In genome-engineered mouse embryonic stem cells, we find that KIF2A localizes to spindle poles during metaphase and regulates spindle length in a manner consistent with its known role as a microtubule minus-end depolymerase. In contrast, during cytokinesis we observe tight binding of KIF2A to intercellular bridge microtubules. At this stage, KIF2A maintains microtubule length and number and controls microtubule acetylation. We propose that the conversion of KIF2A from a depolymerase to a stabilizer is driven by both the inhibition of its ATPase activity, which increases lattice affinity, and a preference for compacted lattices. In turn, KIF2A might maintain the compacted microtubule state at the intercellular bridge, thereby dampening acetylation. As KIF2A depletion causes pluripotency problems and affects mRNA homeostasis, our results furthermore indicate that KIF2A-mediated microtubule stabilization prolongs cytokinesis to maintain pluripotency.