Unknown

Dataset Information

0

Dynein-Dynactin-NuMA clusters generate cortical spindle-pulling forces as a multi-arm ensemble.


ABSTRACT: To position the mitotic spindle within the cell, dynamic plus ends of astral microtubules are pulled by membrane-associated cortical force-generating machinery. However, in contrast to the chromosome-bound kinetochore structure, how the diffusion-prone cortical machinery is organized to generate large spindle-pulling forces remains poorly understood. Here, we develop a light-induced reconstitution system in human cells. We find that induced cortical targeting of NuMA, but not dynein, is sufficient for spindle pulling. This spindle-pulling activity requires dynein-dynactin recruitment by NuMA's N-terminal long arm, dynein-based astral microtubule gliding, and NuMA's direct microtubule-binding activities. Importantly, we demonstrate that cortical NuMA assembles specialized focal structures that cluster multiple force-generating modules to generate cooperative spindle-pulling forces. This clustering activity of NuMA is required for spindle positioning, but not for spindle-pole focusing. We propose that cortical Dynein-Dynactin-NuMA (DDN) clusters act as the core force-generating machinery that organizes a multi-arm ensemble reminiscent of the kinetochore.

SUBMITTER: Okumura M 

PROVIDER: S-EPMC6037482 | BioStudies | 2018-01-01

REPOSITORIES: biostudies

Similar Datasets

2019-01-01 | S-EPMC6525239 | BioStudies
2013-01-01 | S-EPMC3601349 | BioStudies
2012-01-01 | S-EPMC3290711 | BioStudies
2018-01-01 | S-EPMC6214656 | BioStudies
1000-01-01 | S-EPMC3926035 | BioStudies
1000-01-01 | S-EPMC3937087 | BioStudies
1000-01-01 | S-EPMC3744954 | BioStudies
2017-01-01 | S-EPMC5496616 | BioStudies
1000-01-01 | S-EPMC5798331 | BioStudies
1000-01-01 | S-EPMC3986500 | BioStudies