Cytoplasmic dynein-1 cargo diversity is mediated by the combinatorial assembly of FTS-Hook-FHIP complexes

  1. Jenna R Christensen
  2. Agnieszka A Kendrick
  3. Joey B Truong
  4. Adriana Aguilar-Maldonado
  5. Vinit Adani
  6. Monika Dzieciatkowska
  7. Samara L Reck-Peterson  Is a corresponding author
  1. University of California, San Diego, United States
  2. Harvard University, United States
  3. University of Colorado Denver, United States

Abstract

In eukaryotic cells, intracellular components are organized by the microtubule motors cytoplasmic dynein-1 (dynein) and kinesins, which are linked to cargos via adaptor proteins. While ~40 kinesins transport cargo toward the plus end of microtubules, a single dynein moves cargo in the opposite direction. How dynein transports a wide variety of cargos remains an open question. The FTS-Hook-FHIP ('FHF') cargo adaptor complex links dynein to cargo in mammals and fungi. As human cells have three Hooks and four FHIP proteins, we hypothesized that the combinatorial assembly of different Hook and FHIP proteins could underlie dynein cargo diversity. Using proteomic approaches, we determine the protein 'interactome' of each FHIP protein. Live-cell imaging and biochemical approaches show that different FHF complexes associate with distinct motile cargos. These complexes also move with dynein and its cofactor dynactin in single-molecule in vitro reconstitution assays. Complexes composed of FTS, FHIP1B, and Hook1/Hook3 co-localize with Rab5-tagged early endosomes via a direct interaction between FHIP1B and GTP-bound Rab5. In contrast, complexes composed of FTS, FHIP2A and Hook2 colocalize with Rab1A-tagged ER-to-Golgi cargos and FHIP2A is involved in the motility of Rab1A tubules. Our findings suggest that combinatorial assembly of different FTS-Hook-FHIP complexes is one mechanism dynein uses to achieve cargo specificity.

Data availability

Supplementary files 1-3 contain all of the mass spectrometry data.

Article and author information

Author details

  1. Jenna R Christensen

    Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0323-6169
  2. Agnieszka A Kendrick

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

    Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  4. Adriana Aguilar-Maldonado

    Harvard University, Somerville, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1695-1719
  5. Vinit Adani

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

    Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, United States
    Competing interests
    No competing interests declared.
  7. 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

Howard Hughes Medical Institute

  • Samara L Reck-Peterson

National Institutes of Health (R01GM121772)

  • Samara L Reck-Peterson

National Institutes of Health (R35GM141825)

  • Samara L Reck-Peterson

National Institutes of Health (K99GM140269)

  • Jenna R Christensen

American Cancer Society (PF-18-190-01-CCG)

  • Agnieszka A Kendrick

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

Reviewing Editor

  1. Andrew P Carter, MRC Laboratory of Molecular Biology, United Kingdom

Version history

  1. Preprint posted: October 8, 2021 (view preprint)
  2. Received: October 8, 2021
  3. Accepted: December 8, 2021
  4. Accepted Manuscript published: December 9, 2021 (version 1)
  5. Version of Record published: January 5, 2022 (version 2)

Copyright

© 2021, Christensen 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. Jenna R Christensen
  2. Agnieszka A Kendrick
  3. Joey B Truong
  4. Adriana Aguilar-Maldonado
  5. Vinit Adani
  6. Monika Dzieciatkowska
  7. Samara L Reck-Peterson
(2021)
Cytoplasmic dynein-1 cargo diversity is mediated by the combinatorial assembly of FTS-Hook-FHIP complexes
eLife 10:e74538.
https://doi.org/10.7554/eLife.74538

Share this article

https://doi.org/10.7554/eLife.74538

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