Cooperative Accumulation of Dynein-Dynactin at Microtubule Minus-Ends Drives Microtubule Network Reorganization

Cytoplasmic dynein-1 is a minus-end-directed motor protein that transports cargo over long distances and organizes the intracellular microtubule (MT) network. How dynein motor activity is harnessed for these diverse functions remains unknown. Here, we have uncovered a mechanism for how processive dy...

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Bibliographic Details
Published in:Developmental cell 2018-01, Vol.44 (2), p.233-247.e4
Main Authors: Tan, Ruensern, Foster, Peter J., Needleman, Daniel J., McKenney, Richard J.
Format: Article
Language:English
Subjects:
active matter
aster
dynactin
Dynactin Complex - metabolism
dynein
Dyneins - metabolism
microtubule
Microtubule-Associated Proteins - metabolism
Microtubules - metabolism
minus-end
molecular motor
spindle
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Summary:Cytoplasmic dynein-1 is a minus-end-directed motor protein that transports cargo over long distances and organizes the intracellular microtubule (MT) network. How dynein motor activity is harnessed for these diverse functions remains unknown. Here, we have uncovered a mechanism for how processive dynein-dynactin complexes drive MT-MT sliding, reorganization, and focusing, activities required for mitotic spindle assembly. We find that motors cooperatively accumulate, in limited numbers, at MT minus-ends. Minus-end accumulations drive MT-MT sliding, independent of MT orientation, resulting in the clustering of MT minus-ends. At a mesoscale level, activated dynein-dynactin drives the formation and coalescence of MT asters. Macroscopically, dynein-dynactin activity leads to bulk contraction of millimeter-scale MT networks, suggesting that minus-end accumulations of motors produce network-scale contractile stresses. Our data provide a model for how localized dynein activity is harnessed by cells to produce contractile stresses within the cytoskeleton, for example, during mitotic spindle assembly. [Display omitted] •Dynein-dynactin cooperatively form limited-sized motor clusters at MT minus-ends•End clusters provide spatial restriction of force production to MT minus-ends•End clusters slide MTs without orientation bias, leading to minus-end focusing•End clusters produce contractile forces on millimeter-scale MT networks Tan et al. demonstrate how individual cytoplasmic dynein motors organize incoherent collections of microtubules into polarity-sorted structures at varying length scales. Dynein cooperatively accumulates into clusters at microtubule minus-ends, reorganizing microtubules exclusively via clusters, thus providing a molecular explanation for dynein's structural role in mitotic spindle assembly.
ISSN:1534-5807
1878-1551
DOI:10.1016/j.devcel.2017.12.023