Date of Award
2021
Document Type
Dissertation
Degree Name
Ph.D.
Organizational Unit
College of Natural Science and Mathematics, Biological Sciences
First Advisor
Scott A. Barbee
Second Advisor
Robert M. Dores
Third Advisor
Nancy Lorenzon
Fourth Advisor
Daniel Linseman
Fifth Advisor
Michael J. Daniels
Keywords
Aging, Endocytic trafficking, GARP complex, Neurodegeneration, Neurodevelopment, Vps54
Abstract
Vps54 is a subunit of the Golgi-associated retrograde protein (GARP) complex, which is involved in tethering endosome-derived vesicles to the trans-Golgi network (TGN). The “wobbler” mouse is the phenotypic result of a destabilizing point mutation in Vps54. This mutation causes neurodegeneration and is subsequently used as a model for human motor neuron disease. Presently, it is unclear how disruption of GARP complex function leads to motor neuron degeneration. To better understand the role of Vps54 in motor neuron development, function, and age-related neurodegeneration, we disrupted expression of the Vps54 ortholog in Drosophila and examined the impact on larval neuromuscular junction morphology, locomotor function, and longevity. We show that functional null mutants and motor neuron specific knockdown of Vps54 lead to NMJ overgrowth and partial disruption of Syntaxin-16 localization. We also see reduced lifespan and severe locomotor defects in adult flies. We show that Vps54 may be interacting with small GTPases Rab7 and Rab11 at different life stages to further regulate motor neuron development and function. Taken together, these data suggest that Vps54 plays a major role in the development and functional regulation of motor neurons, while additionally interacting with differing endosomal trafficking components associated with disease phenotypes.
Publication Statement
Copyright is held by the author. User is responsible for all copyright compliance.
Rights Holder
Emily Wilkinson
Provenance
Received from ProQuest
File Format
application/pdf
Language
en
File Size
131 pgs
Recommended Citation
Wilkinson, Emily, "The Role of Vps54 in Drosophila melanogaster Neuronal Development and Age Progressive Neurodegeneration" (2021). Electronic Theses and Dissertations. 1882.
https://digitalcommons.du.edu/etd/1882
Copyright date
2021
Discipline
Neurosciences, Neurobiology