TY - JOUR T1 - NuMA Targets Dynein to Microtubule Minus-Ends at Mitosis JF - bioRxiv DO - 10.1101/148692 SP - 148692 AU - Christina L. Hueschen AU - Samuel J. Kenny AU - Ke Xu AU - Sophie Dumont Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/06/11/148692.abstract N2 - To build the spindle at mitosis, motors exert spatially regulated forces on microtubules. We know that dynein pulls on mammalian spindle microtubule minus-ends, and this localized activity at ends is predicted to allow dynein to cluster microtubules into poles. How dynein becomes enriched at minus-ends is not known. Here, we use quantitative imaging and laser ablation to show that NuMA targets dynactin to minus-ends, localizing dynein activity there. NuMA is recruited to new minus-ends independently of dynein and more quickly than dynactin, and both NuMA and dynactin display specific, steady-state binding at minus-ends. NuMA localization to minus-ends requires a C-terminal region outside NuMA’s canonical microtubule binding domain, and it is independent of direct minus-end binders γ-TuRC, CAMSAP1, and KANSL1/3. Both NuMA’s minus-end-binding and dynein-dynactin-binding modules are required to rescue focused, bipolar spindle organization. Thus, NuMA may serve as a mitosis-specific minus-end cargo adaptor, targeting dynein activity to minus-ends to cluster spindle microtubules into poles. ER -