The human cytoplasmic dynein interactome reveals novel activators of motility

  1. Willam B Redwine
  2. Morgan E DeSantis
  3. Ian Hollyer
  4. Zaw Min Htet
  5. Phuoc Tien Tran
  6. Selene K Swanson
  7. Laurence Florens
  8. Michael P Washburn
  9. Samara L Reck-Peterson  Is a corresponding author
  1. University of California, San Diego, United States
  2. Northwestern University, United States
  3. Stowers Institute of Medical Research, United States
  4. Stowers Institute for Medical Research, United States

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 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.

Article and author information

Author details

  1. Willam B Redwine

    Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  2. Morgan E DeSantis

    Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  3. Ian Hollyer

    Feinberg School of Medicine, Northwestern University, Chicago, United States
    Competing interests
    No competing interests declared.
  4. Zaw Min Htet

    Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  5. Phuoc Tien Tran

    Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  6. Selene K Swanson

    Stowers Institute of Medical Research, Kansas City, United States
    Competing interests
    No competing interests declared.
  7. Laurence Florens

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    No competing interests declared.
  8. Michael P Washburn

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7568-2585
  9. Samara L Reck-Peterson

    Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States
    For correspondence
    sreckpeterson@ucsd.edu
    Competing interests
    Samara L Reck-Peterson, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1553-465X

Funding

National Institutes of Health (R01GM121772)

  • Willam B Redwine
  • Phuoc Tien Tran
  • Samara L Reck-Peterson

Howard Hughes Medical Institute (Faculty Scholar)

  • Morgan E DeSantis
  • Samara L Reck-Peterson

Simons Foundation (Faculty Scholar)

  • Morgan E DeSantis
  • Samara L Reck-Peterson

National Institutes of Health (R01GM107214)

  • Ian Hollyer
  • Samara L Reck-Peterson

Jane Coffin Childs Memorial Fund for Medical Research

  • Morgan E DeSantis

National Science Foundation

  • Zaw Min Htet

Stowers Institute for Medical Research

  • Selene K Swanson
  • Laurence Florens
  • Michael P Washburn

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2017, Redwine et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Willam B Redwine
  2. Morgan E DeSantis
  3. Ian Hollyer
  4. Zaw Min Htet
  5. Phuoc Tien Tran
  6. Selene K Swanson
  7. Laurence Florens
  8. Michael P Washburn
  9. Samara L Reck-Peterson
(2017)
The human cytoplasmic dynein interactome reveals novel activators of motility
eLife 6:e28257.
https://doi.org/10.7554/eLife.28257

Share this article

https://doi.org/10.7554/eLife.28257

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