NuMA mediated control of cleavage furrow formation in Human mitosis

The cell division (or mitosis) ensures accurate segregation of the genetic material and other cellular constituents from a mother cell to two daughter cells. Two vital events that occur in mitosis are the separation of the sister chromatids and the formation of the cleavage furrow that ultimately bisects the mother cell into two. The former event is regulated by the NuMA/dynein complex (NuMA-based complex), which is present in the polar membrane regions but absent at the equatorial membrane. We asked why the NuMA-based complex is excluded from the equatorial membrane and the relevance of this exclusion.

Through RNAi-mediated depletion experiments, we showed that the proteins critical for cleavage furrow formation, which include Cyk4, Mklp1, and Ect2, are critical for excluding the NuMA-based complex from the equatorial membrane. Further, we showed that the complex formed by Ect2, Cyk4, and Mklp1 (Ect2-based complex) and NuMA-based complex show mutually exclusive membrane localization (Figure 1). The Ect2-based complex at the equatorial membrane restricts the NuMA-based complex to the polar membrane, which is critical for chromosome separation in anaphase. Similarly, the polar-membrane localized NuMA-based complexes prevent the spreading of Ect2-based complexes to these regions, which ensures proper cleavage furrow formation and cell division. Overall, our work proposes that the physical crowding created by NuMA-based complexes and Ect2-based complexes on different cell membrane regions coordinates chromosome separation and cleavage furrow formation (Figure 1B).