Cell Type-specific Investigation of the FSHR-1 Receptor and its Downstream Pathway Components in Neuromuscular Signaling

David Ryskamp Butler University, Sarah Olofsson Butler University, Amy Godfrey Butler University, Abigail Shores Butler University
Faculty Sponsor(s): Jennifer Kowalski Butler University
G protein-coupled receptors (GPCRs) regulate diverse cellular processes. FSHR-1 is a conserved GPCR controlling metazoan gonad function, but is also expressed in nervous systems. FSHR-1 regulates signaling at the C. elegans neuromuscular junction (NMJ) where a balance of excitatory acetylcholine (ACh) and inhibitory GABA signaling controls muscle contraction. Loss-of-function C. elegans fshr-1 mutants exhibit reduced muscle contraction which is rescued by fshr-1 re-expression in either neuron type. However, the cell type(s) where FSHR-1 is required and the intracellular pathway activated by FSHR-1 at the NMJ are unknown. In the C. elegans germline, FSHR-1 lies upstream of GSA-1 and ACY-1; PKA functions downstream of GSA-1 and ACY-1 for neuromuscular signaling. We hypothesized that in C. elegans GABA and ACh neurons, FSHR-1 controls muscle contraction using the GSA-1/ACY-1/PKA pathway to regulate synaptic vesicle release. To test cell type-specific differences, we performed RNA interference to knock down expression of FSHR-1 pathway components in C. elegans GABA or ACh neurons and analyzed effects on muscle contraction. Knockdown of pathway components in ACh neurons caused decreased muscle contraction with statistically significant decreases seen with knockdown to the synaptic scaffold UNC-10. Knockdown in GABA neurons caused increased muscle contraction with statistically significant increases seen with knockdown of UNC-10 or ACY-1. These data suggest the FSHR-1 pathway promotes synaptic vesicle release in either neuron type. We are now assessing requirements for pathway components in cell type-specific FSHR-1 overexpression backgrounds. Results will provide insight into how FSHR-1 controls NMJ function, aiding understanding of GPCR biology and neuronal signaling.
Oral Presentation

When & Where

09:30 AM
Gallahue Hall 105