12. Examining the Role of FSHR-1, PKA, and Potential Downstream Components in Controlling Neuromuscular Signaling at the NMJ in Caenorhabditis elegans

Abigail Shores Butler University
Faculty Sponsor(s): Jennifer Kowalski Butler University
A tightly regulated balance of excitatory and inhibitory (E:I) neuronal signals is essential for nervous system function. E:I imbalances occur in many diseases like epilepsy and autism. One way neurons regulate this balance is via G-protein coupled receptors (GPCRs). One GPCR, FSHR-1, controls E:I balance at the neuromuscular junction (NMJ) in Caenorhabditis elegans roundworms. At this synapse, excitatory acetylcholine (Ach) signaling and inhibitory gamma-aminobutyric acid (GABA) signaling control muscle contraction. Our previous data suggest FSHR-1 activates a G/ACY-1/Protein Kinase A (PKA) pathway in motor neurons to promote synaptic vesicle release and muscle contraction. PKA regulates many proteins by phosphorylation; however, the specific targets of PKA in the context of FSHR-1 NMJ signaling are unknown. We hypothesized that PKA promotes signaling at the NMJ downstream of FSHR-1 by activating synaptic proteins that may include Ca2+and/or K+ channels, which are required for synaptic vesicle release. We used behavioral assays to measure the effects of mutations in candidate synaptic PKA targets on net signaling for muscle contraction. Loss of function (lf) mutants in egl-36 K+ channels showed increased muscle contraction, whereas unc-2(lf) Ca2+ channel mutants showed decreased contraction. This suggests the corresponding genes for these proteins are essential for normal muscle contraction and E:I balance. Current experiments are using double mutants analyses to test whether these potential PKA substrates act in a genetic pathway with fshr-1. Given the similarity between worm and human genes and nervous systems, this research provides insight into the molecular mechanisms by which GPCRs like FSHR-1 control neuronal signaling.
Poster Presentation

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Irwin Library 3rd Floor