Alejandro Hernandez

ahernandez8@butler.edu

cell-biology , microbiology-molecular-biology , chemistry

Neuromuscular signaling is vital for proper movement and relies on the precise spatial organization of synaptic proteins. Disruptions in this organization can lead to significant deficits, emphasizing the importance of tight regulation of neuromuscular structure and function. We recently discovered the conserved receptor FSHR-1 is a critical regulator of neuromuscular synapses in the roundworm Caenorhabditis elegans. Glycoprotein hormone receptors, including FSHR-1 in worms and its counterparts in mammals, regulate multiple physiological processes, including neuronal signaling. Previous research implicated FSHR-1 in the appropriate localization of vital synaptic proteins, including UNC-10, which governs voltage-gated calcium channel localization at presynaptic sites, and SNB-1/synaptobrevin, a key regulator of synaptic vesicle fusion. However, whether the localization of other associated synaptic proteins is also impacted by FSHR-1 is unknown, as is how FSHR-1, which is not expressed in motor neurons, regulates neuromuscular structure and function. Additional recent data from our lab suggests FSHR-1 acts within IL socket (ILso) glia, to regulate neuromuscular signaling. We hypothesize FSHR-1 acts indirectly within ILso glia to impact neuromuscular structure and function by guiding the spatial distribution of synaptic proteins within motor neurons. To address these hypotheses, we employ genetic manipulations, quantitative fluorescence imaging, and functional assays. To date, our results show fshr-1 mutants have higher amounts of synaptic SPHK-1 proteins in excitatory motor neurons, as seen for UNC-10 and SNB-1. Additional localization results will be presented. This research provides novel insights into the molecular mechanisms of neuromuscular signaling, offering potential therapeutic targets for neuromuscular disorders.