Membrane compartmentalization of Ect2/Cyk4/Mklp1 and NuMA/dynein regulates cleavage furrow formation

Chromosome separation is coupled with cleavage furrow formation during anaphase. Sana, Rajeevan, et al. demonstrate that the mutually exclusive localization of NuMA and Ect2/Cyk4/Mklp1 ensures dynein/dynactin and RhoA at distinct membrane zones to coordinate chromosome separation with cleavage furrow formation. In animal cells, spindle elongation during anaphase is temporally coupled with cleavage furrow formation. Spindle elongation during anaphase is regulated by NuMA/dynein/dynactin complexes that occupy the polar region of the cell membrane and are excluded from the equatorial membrane. How NuMA/dynein/dynactin are excluded from the equatorial membrane and the biological significance of this exclusion remains unknown. Here, we show that the centralspindlin (Cyk4/Mklp1) and its interacting partner RhoGEF Ect2 are required for NuMA/dynein/dynactin exclusion from the equatorial cell membrane. The Ect2-based (Ect2/Cyk4/Mklp1) and NuMA-based (NuMA/dynein/dynactin) complexes occupy mutually exclusive membrane surfaces during anaphase. The equatorial membrane enrichment of Ect2-based complexes is essential for NuMA/dynein/dynactin exclusion and proper spindle elongation. Conversely, NuMA-based complexes at the polar region of the cell membrane ensure spatially confined localization of Ect2-based complexes and thus RhoA. Overall, our work establishes that membrane compartmentalization of NuMA-based and Ect2-based complexes at the two distinct cell surfaces restricts dynein/dynactin and RhoA for coordinating spindle elongation with cleavage furrow formation.

Automated summary

The exclusive localization of NuMA and Ect2/Cyk4/Mklp1 ensures the coordination of spindle elongation and cleavage furrow formation. This coordination is achieved by restricting dynein/dynactin and RhoA to distinct membrane zones.