Kinesin-like protein KIF18A is required for faithful coordination of chromosome congression with cytokinesis

Abstract

The maintenance of genetic integrity in proliferating cells requires the coordinated regulation of DNA replication, chromosome segregation, and cytokinetic abscission. Chromosome-microtubule interactions regulate mitosis, while interactions between the actin cytoskeleton and Myosin IIA dictate cytokinetic abscission. This process, crucial for the equal distribution of the duplicated genome into two daughter cells, occurs perpendicular to the axis of chromosome segregation. However, the mechanism of how microtubule-driven mitosis and actin-associated cytokinesis are precisely coordinated remains poorly understood. This study highlights the role of KIF18A, a kinesin-like protein, in linking kinetochore-microtubule dynamics to cytokinetic axis formation. KIF18A's localization changes through the cell division cycle, from the metaphase plate during chromosome congression to the central spindle in late anaphase, and finally to the spindle midbody in telophase. KIF18A depletion leads to chromosome congression failures and anaphase onset delays. Notably, cells attempting to undergo division in the absence of KIF18A exhibited disruptions in the parallel structure of the central spindle, causing mislocalization of the centralspindlin complex, such as kinesin-like protein KIF23 (also known as MKLP1) and Rac GTPase-activating protein 1 (RACGAP1). These disruptions impair cleavage furrow establishment, causing incomplete cytokinesis and the formation of mononuclear or binucleated cells. Our findings suggest that KIF18A is crucial for coordinating chromosome congression and cytokinesis by regulating the spatial and temporal assembly of the central spindle during late anaphase.

Keywords: KIF18A; central spindle; centralspindlin; chromosome congression; cytokinesis.