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

Indianapolis, IN

Regulation of neuronal signaling (synaptic transmission) is essential for nervous system function. Release of neurotransmitters from presynaptic vesicles, which are necessary for neuronal signaling, are controlled by presynaptic regulatory proteins. 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 or neuropeptides, which regulate neurotransmitter release. Follicle Stimulating hormone receptor (FSHR1) is a conserved GPCR that regulates reproductive processes; FSHR1 is also present in the nervous system, where it regulates neuromuscular signaling in the roundworm Caenorhabditis elegans. Inhibition of fshr1 expression leads to reduced muscle contraction and synaptic vesicles accumulation at presynapses in worms, likely reducing neurotransmitter release; however, the specific pathway activated by FSHR1 to affect synaptic transmission is unknown. UNC 10 (RIM in mammals) is a candidate effector of FSHR1 that regulates synaptic vesicle release at the C. elegans neuromuscular junction. To determine whether FSHR1 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, were imaged on a fluorescence microscope and the level of UNC-10 abundance measured. Changes in synaptic levels of UNC-10 in fshr-1 mutants would indicate that FSHR-1 impacts UNC-10 at neuromuscular synapses, potentially explaining FSHR-1 effects on synaptic transmission. Given the high conservation of gene and nervous system organization with humans, determining the roles of FSHR-1 and UNC-10 may aid understanding of human nervous system disorders.