Date of Award
Neurons communicate at specialized junctions called synapses. Synaptic transmission occurs when presynaptically released neurotransmitters bind to receptors either continuing (excitatory) or stopping (inhibitory) the signal in the postsynaptic cell. Excitatory to inhibitory (E:I) balance is critical for proper neurological function. This balance is achieved through the function of various proteins such as the ubiquitin ligase, the anaphase promoting complex (APC). My thesis project focuses on one potential APC substrate, a G protein-coupled receptor called FSHR-1, and its role in synaptic transmission at the neuromuscular junction (NMJ) in Caenorhabditis elegans. Previous data from our lab and others showed that worms lacking fshr-1 have reduced muscle contraction and that FSHR-1 expression in neurons is sufficient to restore normal NMJ signaling to these animals. I hypothesized that fshr-1 acts presynaptically in one or more neuron subclasses to control NMJ signaling. To identify cells where fshr-1 is expressed, I performed colocalization experiments with animals expressing green fluorescent protein in fshr-1-expressing cells and red fluorescent proteins in specific neuron subclasses. Experiments testing fshr-1 expression in sensory neurons in the C. elegans head and tail showed no overlap of red and green fluorescence, indicating fshr-1 is not expressed in these cells. Similarly, glutamatergic interneurons, cholinergic motor neurons, and GABAergic motor neurons also showed no fshr-1 expression. I am currently creating strains to do colocalization with pharyngeal neurons in the head. I also made a fluorescently tagged FSHR-1 protein to be used to determine FSHR-1 subcellular localization. This tagged FSHR-1 will be assessed for co-localization with a red fluorescent protein-labeled synaptic vesicle protein. Understanding how and where FSHR-1 is acting will allow us to better understand its role and relation to the APC in E:I balance, which may further our understanding of the ubiquitin system and E:I imbalances in neurological diseases.
Cherry, Kyle, "Investigation of the localization and expression of the G-protein coupled receptor FSHR-1 in C. elegans neurons" (2016). Undergraduate Honors Thesis Collection. 340.