Author ORCID Identifier

https://orcid.org/0000-0003-0320-8432

Date Available

3-27-2024

Year of Publication

2022

Degree Name

Master of Science in Medical Sciences (MSMS)

Document Type

Master's Thesis

College

Medicine

Department/School/Program

Medical Sciences

First Advisor

Dr. Salvatore J. Cherra III

Abstract

Precise coordination of the activity and transmission in excitatory and inhibitory neural circuits is essential for healthy information flow. Synaptic scaffolding proteins play a key role in the regulation of circuit activity through the localization and organization of receptors, channels, and other synaptic machinery to facilitate signal transduction. Using the C. elegans motor circuit which has both cholinergic (excitatory) and GABAergic (inhibitory) inputs onto muscles, we revealed an unexplored role of a family of scaffolding molecules known as membrane palmitoylated proteins (MPPs). Here, we examined magu-3, a C. elegans ortholog within the membrane palmitoylated protein family, using GFP tagging to identify its expression patterns and aldicarb induced paralysis to examine its neuronal function. We found that magu-3 is expressed throughout the C. elegans nervous system, including motor neurons, and that magu-3 mutants exhibit increased cholinergic activity at the neuromuscular junction. Furthermore, we revealed a novel, complex interaction between mutants of the dystrobrevin ortholog, dyb-1, and magu-3 mutants. This study establishes the foundation for investigating neuronal mechanisms of MPPs using C. elegans and demonstrates that the MPP MAGU-3 regulates locomotor circuit function.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2022.047

Funding Information

This study was supported by the National Institutes of Health Pathway to Independence Award (NS097638) and the University of Kentucky College of Medicine (Start-up funding) from 2019 - 2021.

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