Journal article
Cytoplasmic Dynein Transports Axonal Microtubules in a Polarity-Sorting Manner
Cell reports (Cambridge), v 19(11), pp 2210-2219
13 Jun 2017
PMID: 28614709
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Axonal microtubules are predominantly organized into a plus-end-out pattern. Here, we tested both experimentally and with computational modeling whether a motor-based polarity-sorting mechanism can explain this microtubule pattern. The posited mechanism centers on cytoplasmic dynein transporting plus-end-out and minus-end-out microtubules into and out of the axon, respectively. When cytoplasmic dynein was acutely inhibited, the bi-directional transport of microtubules in the axon was disrupted in both directions, after which minus-end-out microtubules accumulated in the axon over time. Computational modeling revealed that dynein-mediated transport of microtubules can establish and preserve a predominantly plus-end-out microtubule pattern as per the details of the experimental findings, but only if a kinesin motor and a static cross-linker protein are also at play. Consistent with the predictions of the model, partial depletion of TRIM46, a protein that cross-links axonal microtubules in a manner that influences their polarity orientation, leads to an increase in microtubule transport.
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•Cytoplasmic dynein transports microtubules bi-directionally in the axon•Dynein-based transport sorts microtubules according to their polarity orientation•Computational modeling predicts other molecular players as well as dynein•TRIM46 acts as a cross-linker that influences microtubule transport
Rao et al. show that the plus-end-out microtubule polarity pattern of the axon can be explained by a polarity-sorting mechanism driven by cytoplasmic dynein, together with the participation of other players that include an opposing motor and a cross-linker protein.
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Details
- Title
- Cytoplasmic Dynein Transports Axonal Microtubules in a Polarity-Sorting Manner
- Creators
- Anand N Rao - Department of Neurobiology and Anatomy, Drexel University, Philadelphia, PA 19129, USAAnkita Patil - Department of Neurobiology and Anatomy, Drexel University, Philadelphia, PA 19129, USAMark M Black - Department of Anatomy and Cell Biology, Temple University, Philadelphia, PA 19140, USAErin M Craig - Department of Physics, Central Washington University, Ellensburg, WA 98926, USAKenneth A Myers - Department Biological Sciences, University of the Sciences, Philadelphia, PA 19104, USAHoward T Yeung - Department of Physics, Central Washington University, Ellensburg, WA 98926, USAPeter W Baas - Department of Neurobiology and Anatomy, Drexel University, Philadelphia, PA 19129, USA
- Publication Details
- Cell reports (Cambridge), v 19(11), pp 2210-2219
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000403207700005
- Scopus ID
- 2-s2.0-85020691977
- Other Identifier
- 991014877957204721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology