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Elife. 2017 Jan 7;6. pii: e23367. doi: 10.7554/eLife.23367.

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

Author information

1
Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, United States.
2
Laboratory of Membrane Trafficking Mechanisms, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai, Japan.
3
Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

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.

KEYWORDS:

Drosophila metamorphosis; Rab GTPase; T-tubule; autophagosome-lysosome fusion; autophagy; cell biology; developmental biology; muscle fiber; stem cells

PMID:
28063257
PMCID:
PMC5249261
DOI:
10.7554/eLife.23367
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

IK-H: Reviewing editor, eLife. The other authors declare that no competing interests exist.

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