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

Naonobu Fujita, Wilson Huang, Tzu Han Lin, Jean Francois Groulx, Steve Jean, Jen Nguyen, Yoshihiko Kuchitsu, Ikuko Koyama-Honda, Noboru Mizushima, Mitsunori Fukuda, Amy A. Kiger

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    32 Citations (Scopus)

    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.

    Original languageEnglish
    Article numbere23367
    JournaleLife
    Volume6
    DOIs
    Publication statusPublished - 2017 Jan 7

    ASJC Scopus subject areas

    • Neuroscience(all)
    • Immunology and Microbiology(all)
    • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Fujita, N., Huang, W., Lin, T. H., Groulx, J. F., Jean, S., Nguyen, J., Kuchitsu, Y., Koyama-Honda, I., Mizushima, N., Fukuda, M., & Kiger, A. A. (2017). Genetic screen in drosophila muscle identifies autophagy-mediated T-tubule remodeling and a Rab2 role in autophagy. eLife, 6, [e23367]. https://doi.org/10.7554/eLife.23367