Mechanisms of spindle positioning and elongation in human cells

The positioning and the elongation of the mitotic spindle must be carefully regulated. In human cells, the evolutionary conserved proteins LGN/Gαi1-3 anchor NuMA/dynein to the membrane in metaphase, thus ensuring proper spindle positioning. The mechanisms governing cortical localization of NuMA/dynein during anaphase remain elusive. We discovered that cortical levels of dynein markedly increase as cells transit from metaphase to anaphase in a NuMA dependent manner. This increase in cortical dynein is crucial for proper spindle elongation during anaphase. Notable, we uncovered that LGN/Gαi1-3 are dispensable for NuMA-dependent cortical dynein enrichment during anaphase. Furthermore, our work revealed that NuMA directly interacts with membrane phosphoinositides in vitro and in vivo, and cortical localization of NuMA during anaphase is dependent on these lipids. In summary, our study illustrates novel mechanisms by which NuMA serves as a critical player that links cell cycle progression with proper spindle behavior to ensure faithful execution of mitosis.