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The Human Cytoplasmic Dynein Interactome Reveals Novel Activators of Motility

William B. Redwine, Morgan E. DeSantis, Ian Hollyer, Zaw Min Htet, Phuoc Tien Tran, Selene K. Swanson, Laurence Florens, Michael P. Washburn, View ORCID ProfileSamara L. Reck-Peterson
doi: https://doi.org/10.1101/143743
William B. Redwine
1Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, 92093
2Department of Cell Biology, Harvard Medical School, Boston, MA 02115
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Morgan E. DeSantis
1Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, 92093
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Ian Hollyer
1Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, 92093
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Zaw Min Htet
1Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, 92093
3Biophysics Graduate Program, Harvard Medical School, Boston, MA 92105
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Phuoc Tien Tran
1Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, 92093
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Selene K. Swanson
4Stowers Institute for Medical Research, Kansas City, MO 64110
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Laurence Florens
4Stowers Institute for Medical Research, Kansas City, MO 64110
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Michael P. Washburn
4Stowers Institute for Medical Research, Kansas City, MO 64110
5Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160
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Samara L. Reck-Peterson
1Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, 92093
2Department of Cell Biology, Harvard Medical School, Boston, MA 02115
6Division of Biological Sciences, Cell and Developmental Biology Section, University of California San Diego, La Jolla, CA 92093
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  • ORCID record for Samara L. Reck-Peterson
  • For correspondence: sreckpeterson@ucsd.edu
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ABSTRACT

In human cells, cytoplasmic dynein-1 is essential for long-distance transport of many cargos, including organelles, RNAs, proteins, and viruses, towards microtubule minus ends. To understand how a single motor achieves cargo specificity, we identified the human dynein interactome or “transportome” by attaching a promiscuous biotin ligase (“BioID”) to seven components of the dynein machinery, including a subunit of the essential cofactor dynactin. This method reported spatial information about the large cytosolic dynein/dynactin complex in living cells. To achieve maximal motile activity and to bind its cargos, human dynein/dynactin requires “activators”, of which only five have been described. We developed methods to identify new activators in our BioID data, and discovered that ninein and ninein-like are a new family of dynein activators. Analysis of the protein interactomes for six activators, including ninein and ninein-like, suggests that each dynein activator has multiple cargos.

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Posted May 30, 2017.
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The Human Cytoplasmic Dynein Interactome Reveals Novel Activators of Motility
William B. Redwine, Morgan E. DeSantis, Ian Hollyer, Zaw Min Htet, Phuoc Tien Tran, Selene K. Swanson, Laurence Florens, Michael P. Washburn, Samara L. Reck-Peterson
bioRxiv 143743; doi: https://doi.org/10.1101/143743
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The Human Cytoplasmic Dynein Interactome Reveals Novel Activators of Motility
William B. Redwine, Morgan E. DeSantis, Ian Hollyer, Zaw Min Htet, Phuoc Tien Tran, Selene K. Swanson, Laurence Florens, Michael P. Washburn, Samara L. Reck-Peterson
bioRxiv 143743; doi: https://doi.org/10.1101/143743

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