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

    研究成果: Article査読

    58 被引用数 (Scopus)

    抄録

    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.

    本文言語English
    論文番号e23367
    ジャーナルeLife
    6
    DOI
    出版ステータスPublished - 2017 1月 7

    ASJC Scopus subject areas

    • 神経科学(全般)
    • 免疫学および微生物学(全般)
    • 生化学、遺伝学、分子生物学(全般)

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