Genetic screen in Drosophila muscle identifies autophagy-mediated T-tubule remodeling and a Rab2 role in autophagy
- University of California, San Diego, United States
- Tohoku University, Japan
- The University of 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.
Article and author information
Author details
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
- Hong Zhang, Institute of Biophysics, Chinese Academy of Sciences, China
Version history
- Received: November 16, 2016
- Accepted: December 17, 2016
- Accepted Manuscript published: January 7, 2017 (version 1)
- 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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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
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