NuMA is a mitotic adaptor protein that activates dynein and connects it to microtubule minus ends

Abstract

Nuclear mitotic apparatus protein (NuMA) is indispensable for the mitotic functions of the major microtubule minus-end directed motor cytoplasmic dynein 1. NuMA and dynein are both essential for correct spindle pole organization. How these proteins cooperate to gather microtubule minus ends at spindle poles remains unclear. Here, we use microscopy-based in vitro reconstitutions to demonstrate that NuMA is a dynein adaptor, activating processive dynein motility together with dynein's cofactors dynactin and Lissencephaly-1 (Lis1). Additionally, we find that NuMA binds and stabilizes microtubule minus ends, allowing dynein/dynactin/NuMA to transport microtubule minus ends as cargo to other minus ends. We further show that the microtubule-nucleating γ-tubulin ring complex (γTuRC) hinders NuMA binding and that NuMA only caps minus ends of γTuRC-nucleated microtubules after γTuRC release. These results provide new mechanistic insight into how dynein, dynactin, NuMA, and Lis1 together with γTuRC and uncapping proteins cooperate to organize spindle poles in cells.