Activation and regulation of the dynein-dynactin-NuMA complex

Merve Aslan; Ennio A d'Amico; Nathan H Cho; Aryan Taheri; Juan M Perez-Bertoldi; Yuanchang Zhao; Xinyue Zhong; Madeline Blaauw; Andrew P Carter; Sophie Dumont; Ahmet Yildiz

doi:10.1038/s41589-026-02156-7

Activation and regulation of the dynein-dynactin-NuMA complex

Nat Chem Biol. 2026 Mar 16. doi: 10.1038/s41589-026-02156-7. Online ahead of print.

Authors

Merve Aslan^#¹, Ennio A d'Amico^#², Nathan H Cho^#^{3

4}, Aryan Taheri⁵, Juan M Perez-Bertoldi¹, Yuanchang Zhao⁵, Xinyue Zhong¹, Madeline Blaauw^{4

6}, Andrew P Carter⁷, Sophie Dumont^{8

9

10

11

12}, Ahmet Yildiz^{13

14

15}

Affiliations

¹ Biophysics Graduate Group, University of California, Berkeley, Berkeley, CA, USA.
² MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
³ Tetrad Graduate Program, University of California, Berkeley, San Francisco, CA, USA.
⁴ Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
⁵ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
⁶ UCB-UCSF Bioengineering Graduate Program, San Francisco, CA, USA.
⁷ MRC Laboratory of Molecular Biology, Cambridge, United Kingdom. cartera@mrc-lmb.cam.ac.uk.
⁸ Tetrad Graduate Program, University of California, Berkeley, San Francisco, CA, USA. sophie.dumont@ucsf.edu.
⁹ Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA. sophie.dumont@ucsf.edu.
¹⁰ UCB-UCSF Bioengineering Graduate Program, San Francisco, CA, USA. sophie.dumont@ucsf.edu.
¹¹ Department of Biochemistry & Biophysics, University of California, San Francisco, San Francisco, CA, USA. sophie.dumont@ucsf.edu.
¹² Chan Zuckerberg Biohub, San Francisco, CA, USA. sophie.dumont@ucsf.edu.
¹³ Biophysics Graduate Group, University of California, Berkeley, Berkeley, CA, USA. yildiz@berkeley.edu.
¹⁴ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA. yildiz@berkeley.edu.
¹⁵ Physics Department, University of California, Berkeley, Berkeley, CA, USA. yildiz@berkeley.edu.

^# Contributed equally.

PMID: 41840068
DOI: 10.1038/s41589-026-02156-7

Abstract

During cell division, the nuclear mitotic apparatus protein (NuMA) orchestrates the focusing of microtubule minus-ends in spindle poles and cortical force generation on astral microtubules by interacting with dynein motors, microtubules and other cellular factors. Here we used in vitro reconstitution, cryo-electron microscopy and live-cell imaging to understand the mechanism and regulation of NuMA. We determined the structure of the processive dynein-dynactin-NuMA complex (DDN) and showed that the NuMA N terminus drives dynein motility in vitro and facilitates dynein-mediated transport in live cells. The C terminus of NuMA directly binds and suppresses the dynamics of the microtubule minus-end. Full-length NuMA is autoinhibited for its interactions with dynein and microtubules, whereas mitotically phosphorylated NuMA activates dynein in vitro and interphase cells. Together with dynein, activated full-length NuMA focuses microtubule minus-ends into aster-like structures. These results provide critical insights into the activation of NuMA and dynein for their mitotic functions.

Abstract

Grants and funding