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Genetic screen in Drosophila muscle identifies autophagy-mediated T-tubule remodeling and a Rab2 role in autophagy

  1. Naonobu Fujita  Is a corresponding author
  2. Wilson Huang
  3. Tzu-han Lin
  4. Jean-Francois Groulx
  5. Steve Jean
  6. Yoshihiko Kuchitsu
  7. Ikuko Koyama-Honda
  8. Noboru Mizushima
  9. Mitsunori Fukuda
  10. Amy A Kiger  Is a corresponding author
  1. University of California, San Diego, United States
  2. Tohoku University, Japan
  3. The University of Tokyo, Japan
Research Article
  • Cited 25
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Cite this article as: eLife 2017;6:e23367 doi: 10.7554/eLife.23367

Abstract

Transverse (T)-tubules make-up a specialized network of tubulated muscle cell membranes involved in excitation-contraction coupling for power of contraction. Little is known about how T-tubules maintain highly organized structures and contacts throughout the contractile system despite the ongoing muscle remodeling that occurs with muscle atrophy, damage and aging. We uncovered an essential role for autophagy in T-tubule remodeling with genetic screens of a developmentally regulated remodeling program in Drosophila abdominal muscles. Here, we show that autophagy is both upregulated with and required for progression through T-tubule disassembly stages. Along with known mediators of autophagosome-lysosome fusion, our screens uncovered an unexpected shared role for Rab2 with a broadly conserved function in autophagic clearance. Rab2 localizes to autophagosomes and binds to HOPS complex members, suggesting a direct role in autophagosome tethering/fusion. Together, the high membrane flux with muscle remodeling permits unprecedented analysis both of T-tubule dynamics and fundamental trafficking mechanisms.

Article and author information

Author details

  1. Naonobu Fujita

    Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, United States
    For correspondence
    naonobu.fujita.b8@tohoku.ac.jp
    Competing interests
    No competing interests declared.
  2. Wilson Huang

    Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, United States
    Competing interests
    No competing interests declared.
  3. Tzu-han Lin

    Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, United States
    Competing interests
    No competing interests declared.
  4. Jean-Francois Groulx

    Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, United States
    Competing interests
    No competing interests declared.
  5. Steve Jean

    Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, United States
    Competing interests
    No competing interests declared.
  6. Yoshihiko Kuchitsu

    Laboratory of Membrane Trafficking Mechanisms, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai, Japan
    Competing interests
    No competing interests declared.
  7. Ikuko Koyama-Honda

    Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, Tokyo, Japan
    Competing interests
    No competing interests declared.
  8. Noboru Mizushima

    Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, Tokyo, Japan
    Competing interests
    Noboru Mizushima, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6258-6444
  9. Mitsunori Fukuda

    Laboratory of Membrane Trafficking Mechanisms, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai, Japan
    Competing interests
    No competing interests declared.
  10. Amy A Kiger

    Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, United States
    For correspondence
    akiger@ucsd.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4300-176X

Funding

American Heart Association (Innovative Research Grant,15IRG22830029)

  • Amy A Kiger

Japan Society for the Promotion of Science (Postdoctoral Fellowship)

  • Naonobu Fujita

Uehara Memorial Foundation (Postdoctoral Fellowship)

  • Naonobu Fujita

Kanae Foundation (Postdoctoral Fellowship)

  • Naonobu Fujita

Scientific Research on Innovative Areas (Grant-in-Aid for Scientific Research,25111005)

  • Noboru Mizushima

Ministry of Education, Culture, Sports, Science, and Technology (Grant-in-Aid for Scientific Research,16H01189)

  • Mitsunori Fukuda

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

Reviewing Editor

  1. Hong Zhang, Institute of Biophysics, Chinese Academy of Sciences, China

Publication history

  1. Received: November 16, 2016
  2. Accepted: December 17, 2016
  3. Accepted Manuscript published: January 7, 2017 (version 1)
  4. Version of Record published: January 20, 2017 (version 2)

Copyright

© 2017, Fujita 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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