RRC ID 48561
Author Fujita N, Huang W, Lin TH, Groulx JF, Jean S, Nguyen J, Kuchitsu Y, Koyama-Honda I, Mizushima N, Fukuda M, Kiger AA.
Title Genetic screen in Drosophila muscle identifies autophagy-mediated T-tubule remodeling and a Rab2 role in autophagy.
Journal Elife
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.
Volume 6
Published 2017-1-7
DOI 10.7554/eLife.23367
PII e23367
PMID 28063257
PMC PMC5249261
MeSH Animals Autophagy / genetics* Drosophila Proteins / genetics Drosophila Proteins / metabolism Drosophila melanogaster / genetics* Drosophila melanogaster / growth & development Drosophila melanogaster / metabolism Gene Expression Profiling Gene Expression Regulation, Developmental* Lysosomes / metabolism Membrane Fusion Morphogenesis / genetics* Muscles / metabolism* Phagosomes / metabolism Protein Isoforms / genetics Protein Isoforms / metabolism Protein Transport Qa-SNARE Proteins / genetics Qa-SNARE Proteins / metabolism R-SNARE Proteins / genetics R-SNARE Proteins / metabolism RNA, Small Interfering / genetics RNA, Small Interfering / metabolism SNARE Proteins / genetics SNARE Proteins / metabolism Signal Transduction rab GTP-Binding Proteins / genetics rab GTP-Binding Proteins / metabolism rab2 GTP-Binding Protein / antagonists & inhibitors rab2 GTP-Binding Protein / genetics rab2 GTP-Binding Protein / metabolism* rab7 GTP-Binding Proteins
IF 7.08
Times Cited 35
DNA material pEF-T7-mouse Vps39 (RDB14679) pEF-T7-mouse Vps41 (RDB14680).