NuMA: a nuclear protein involved in mitotic centrosome function

Nuclear mitotic apparatus protein, NuMA, is an abundant 240 kDa protein with microtubule (MT) binding capacity via its carboxyl terminal region. Structurally, it has been shown to be a double-strand coiled-coil that has a high potential to form filamentous polymers. During interphase, NuMA locates within the nucleus but rapidly redistributes to the separating centrosomes during early mitosis. Xenopus NuMA associates with MT minus end-directed motor cytoplasmic dynein and its motility-activating complex dynactin at mitotic centrosomal regions. This NuMA-motor complex binds the free ends of MTs, converging and tethering spindle MT ends to the poles. A similar scenario appears to be true in higher vertebrates as well. As a mitotic centrosomal component, NuMA is essential for the organization and stabilization of spindle poles from early mitosis until at least the onset of anaphase. The cell cycle-dependent distribution and function of NuMA is regulated by phosphorylation and dephosphorylation, and p34/CDC2 activity is important to the mitotic role of NuMA. This review summarizes data about the structural features and mitotic function of NuMA with particular emphasis on the newly discovered NuMA-motor complex in spindle organization. Furthermore, NuMA may represent a large group of proteins whose mitotic function is sequestered in the nucleus during interphase.