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| Title | Activation and regulation of the dynein-dynactin-NuMA complex. |
|---|---|
| Journal, issue, pages | Nat Chem Biol, Year 2026 |
| Publish date | Mar 16, 2026 |
Authors | 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 / ![]() |
| PubMed 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 ...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. |
External links | Nat Chem Biol / PubMed:41840068 |
| Methods | EM (single particle) |
| Resolution | 6.53 - 6.78 Å |
| Structure data | EMDB-52171, PDB-9hhl: ![]() EMDB-52172: Dynactin pointed end in complex with NuMA |
| Chemicals | ![]() ChemComp-ADP: ![]() ChemComp-ATP: ![]() ChemComp-ZN: |
| Source |
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Keywords | MOTOR PROTEIN / transport |
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