Publication Date
10-12-2021
Document Type
Article
Organizational Units
College of Natural Science and Mathematics, Biological Sciences
Keywords
Vps54, Drosophila melanogaster, Motor neuron (MN) degeneration
Abstract
Vps54 is an integral subunit of the Golgi-associated retrograde protein (GARP) complex, which is involved in tethering endosome-derived vesicles to the trans-Golgi network (TGN). A destabilizing missense mutation in Vps54 causes the age-progressive motor neuron (MN) degeneration, muscle weakness, and muscle atrophy observed in the wobbler mouse, an established animal model for human MN disease. It is currently unclear how the disruption of Vps54, and thereby the GARP complex, leads to MN and muscle phenotypes. To develop a new tool to address this question, we have created an analogous model in Drosophila by generating novel loss-of-function alleles of the fly Vps54 ortholog (scattered/scat). We find that null scat mutant adults are viable but have a significantly shortened lifespan. Like phenotypes observed in the wobbler mouse, we show that scat mutant adults are male sterile and have significantly reduced body size and muscle area. Moreover, we demonstrate that scat mutant adults have significant age-progressive defects in locomotor function. Interestingly, we see sexually dimorphic effects, with scat mutant adult females exhibiting significantly stronger phenotypes. Finally, we show that scat interacts genetically with rab11 in MNs to control age-progressive muscle atrophy in adults. Together, these data suggest that scat mutant flies share mutant phenotypes with the wobbler mouse and may serve as a new genetic model system to study the cellular and molecular mechanisms underlying MN disease.
Copyright Statement / License for Reuse
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Statement
This article was originally published as:
Wilkinson, E. C., Starke, E. L., & Barbee, S. A. (2021). Vps54 regulates lifespan and locomotor behavior in adult drosophila melanogaster. Frontiers in Genetics, 12(Article 762012). DOI: 10.3389/fgene.2021.762012
Rights Holder
Emily C. Wilkinson, Emily L. Starke, Scott A. Barbee
Provenance
Received from author
File Format
application/pdf
Language
English (eng)
Extent
10 pgs
File Size
1.7 MB
Publication Title
Frontiers in Genetics
Volume
12
First Page
1
Last Page
10
Recommended Citation
Wilkinson, Emily C.; Starke, Emily L.; and Barbee, Scott A., "Vps54 Regulates Lifespan and Locomotor Behavior in Adult Drosophila Melanogaster" (2021). Biological Sciences: Faculty Scholarship. 65.
https://digitalcommons.du.edu/biological_sciences_faculty/65
https://doi.org/10.3389/fgene.2021.762012
DOI Link
https://doi.org/10.3389/fgene.2021.762012
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Biology Commons, Genetics Commons, Molecular Genetics Commons