Regulators of Autophagosome Formation in Drosophila Muscles

View/ Open
Published Version
https://doi.org/10.1371/journal.pgen.1005006Metadata
Show full item recordCitation
Zirin, Jonathan, Joppe Nieuwenhuis, Anastasia Samsonova, Rong Tao, and Norbert Perrimon. 2015. “Regulators of Autophagosome Formation in Drosophila Muscles.” PLoS Genetics 11 (2): e1005006. doi:10.1371/journal.pgen.1005006. http://dx.doi.org/10.1371/journal.pgen.1005006.Abstract
Given the diversity of autophagy targets and regulation, it is important to characterize autophagy in various cell types and conditions. We used a primary myocyte cell culture system to assay the role of putative autophagy regulators in the specific context of skeletal muscle. By treating the cultures with rapamycin (Rap) and chloroquine (CQ) we induced an autophagic response, fully suppressible by knockdown of core ATG genes. We screened D. melanogaster orthologs of a previously reported mammalian autophagy protein-protein interaction network, identifying several proteins required for autophagosome formation in muscle cells, including orthologs of the Rab regulators RabGap1 and Rab3Gap1. The screen also highlighted the critical roles of the proteasome and glycogen metabolism in regulating autophagy. Specifically, sustained proteasome inhibition inhibited autophagosome formation both in primary culture and larval skeletal muscle, even though autophagy normally acts to suppress ubiquitin aggregate formation in these tissues. In addition, analyses of glycogen metabolic genes in both primary cultured and larval muscles indicated that glycogen storage enhances the autophagic response to starvation, an important insight given the link between glycogen storage disorders, autophagy, and muscle function.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334200/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:14065467
Collections
- HMS Scholarly Articles [17791]
Contact administrator regarding this item (to report mistakes or request changes)