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.
","abstract_html":"<p>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.</p>","abstract_has_math":false,"creators":["Wilkinson, Emily"],"institution":null,"degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Scott A. Barbee","Robert M. Dores","Nancy Lorenzon","Daniel Linseman","Michael J. Daniels"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2021,"date_issued":"2021-01-01T08:00:00Z","date_published":"2021-01-01T08:00:00Z","updated_at":"2026-07-24T02:03:12Z","subjects":["Aging","Endocytic trafficking","GARP complex","Neurodegeneration","Neurodevelopment","Vps54","Developmental Neuroscience","Life Sciences","Neuroscience and Neurobiology","Other Neuroscience and Neurobiology"],"languages":["en"],"rights":["Copyright is held by the author. User is responsible for all copyright compliance.
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"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["The Role of Vps54 in Drosophila melanogaster Neuronal Development and Age Progressive Neurodegeneration"]}]}],"canonical_facts":{"dc:contributor":["Scott A. Barbee","Robert M. Dores","Nancy Lorenzon","Daniel Linseman","Michael J. Daniels"],"dc:creator":["Wilkinson, Emily"],"dc:date.available":["2021-07-16T07:00:00Z"],"dc:description.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.
"],"dc:format":["application/pdf"],"dc:identifier":["https://digitalcommons.du.edu/etd/1882"],"dc:language":["en"],"dc:rights":["Copyright is held by the author. User is responsible for all copyright compliance.
"],"dc:subject":["Aging","Endocytic trafficking","GARP complex","Neurodegeneration","Neurodevelopment","Vps54","Developmental Neuroscience","Life Sciences","Neuroscience and Neurobiology","Other Neuroscience and Neurobiology"],"dc:title":["The Role of Vps54 in Drosophila melanogaster Neuronal Development and Age Progressive Neurodegeneration"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."]},"updated_at":"2026-07-24T02:03:12Z"}