18. Investigation of G protein-coupled Receptor FSHR1 in Regulation of UNC-10 RIM Synaptic Localization in C. elegans

Morgan Buckley Butler University
Faculty Sponsor(s): Jennifer Kowalski Butler University
Regulation of neuronal signaling is essential for nervous system function. G protein-coupled receptors (GPCRs) are a class of synaptic membrane proteins with diverse functions across eukaryotes and are targets of many drugs. In the nervous system, GPCRs are receptors for neurotransmitters and regulate neurotransmitter release. Follicle Stimulating hormone receptor (FSHR) is a conserved GPCR present in the nervous system of Caenorhabditis elegans, where it regulates neuromuscular signaling. Inhibition of fshr-1 expression causes reduced muscle contraction and synaptic vesicle accumulation at motor neuron presynapses in worms, likely reducing neurotransmitter release. The specific pathway activated by FSHR-1 to affect synaptic transmission is unknown. UNC-10 (RIM in mammals) is a candidate FSHR-1 effector that regulates synaptic vesicle release at the C. elegans neuromuscular junction. To determine whether FSHR-1 regulates UNC-10 synaptic localization, the dorsal nerve cords of wild type and fshr-1 loss-of-function mutant worms, in which UNC-10 is tagged with green fluorescent protein (GFP), were imaged on a fluorescence microscope and the level of UNC-10 abundance measured. fshr-1 mutant worms exhibited elevated levels of UNC-10::GFP intensity and increased axonal fluorescence (p = 0.02, 0.02) at cholinergic presynapses. However, UNC-10::Cherry expression in GABAergic neurons of fshr-1 mutants showed no significant differences from those of wild type animals, in (p>0.05). Together, these data suggest fshr-1 may be required to specifically restrict the localization of UNC-10 to synapses in cholinergic neurons. Given the conservation of C. elegans and human genes and nervous system organization, determining the function of FSHR-1 may aid understanding of human neurological disorders.
Biology
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Irwin Library 3rd Floor