Investigation of FSHR-1 Protein Function in Regulating Synaptic Transmission in C. elegans

Indianapolis, IN

Neuronal communication (synaptic transmission) is critical for nervous system function. This communication occurs at specialized junctions called synapses where chemical neurotransmitters signal from presynaptic to postsynaptic cells. Additional signaling via neuropeptide molecules fine-tunes synaptic communication. G Protein-Coupled Receptors (GPCRs) are a large family of transmembrane receptor proteins that bind extracellular neurotransmitters and neuropeptides to activate intracellular signaling pathways. My project investigates the function of one GPCR and potential neuropeptide receptor, FSHR-1, in regulating synaptic transmission at the neuromuscular junction (NMJ) in Caenorhabditis. elegans roundworms, which share conservation of nervous system structure and function with humans. Worms lacking fshr-1 have reduced muscle contraction at the NMJ; however, the mechanism by which FSHR-1 controls signaling at this synapse is unknown. I hypothesized that FSHR-1 is a neuropeptide receptor that acts in presynaptic motor neurons to modulate NMJ transmission. Initial genetic and behavioral analyses of fshr-1 and neuropeptide signaling mutants, indicate that fshr-1 does not interact with neuropeptide signaling, however future studies are needed to fully explore a potential interaction. With regard to downstream targets of FSHR-1 signaling, behavioral results indicate that the adenylyl cyclase enzyme ACY-1 , may works in the same genetic pathway as FSHR-1 to control muscle contraction. I currently am exploring other downstream targets of FSHR-1, as well as imaging synaptic vesicles in cholinergic and GABAergic motor neurons of fshr-1 mutants. These results will provide information regarding the potential neuronal function of FSHR-1 and increase our understanding of GPCR biology, which may provide insight into human neurological diseases.