Biology
Investigation of the FSHR-1 Receptor and its Downstream Pathway Components in Neuromuscular Signaling
Document Type
Poster Presentation
Location
Indianapolis, IN
Start Date
13-4-2018 2:30 PM
End Date
13-4-2018 4:00 PM
Sponsor
Jennifer Kowalski (Butler University)
Description
G protein-coupled receptors (GPCRs) regulate diverse processes in cells ranging from heart cells to neurons. FSHR-1 is a conserved GPCR that controls reproductive processes in metazoans, but is also expressed in nervous systems, such as that of Caenorhabditis elegans, Behavioral data indicate that FSHR-1 regulates signaling at the C. elegans neuromuscular junction (NMJ) where a balance of acetylcholine (ACh) and GABA signaling controls muscle contraction. Loss-of-function (lf) C. elegans mutants in fshr-1 exhibit reduced muscle contraction, which is rescued by re-expression of fshr-1 in either neuron type. However, the pathways 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 to control neuromuscular signaling. We hypothesized that in C. elegans GABA and ACh neurons, FSHR-1 promotes muscle contraction using the GSA-1/ACY-1/PKA pathway to regulate synaptic vesicle release. We used paralysis induced by aldicarb, an acetylcholinesterase inhibitor, to measure neuromuscular signaling in worms with mutations in suspected FSHR-1 pathway components. Worms with gain-of-function (gf) mutations in gsa-1, acy-1, or pka paralyzed faster on aldicarb than wild type controls. Worms with fshr-1(lf) and gsa-1(gf) or acy-1(gf) had paralysis rates comparable to acy-1(gf) or gsa-1(gf) single mutants, suggesting PKA, ACY-1, and GSA-1 influence neuromuscular signaling downstream of FSHR-1. Ongoing experiments are testing whether the transcription factor CREB or the active zone protein UNC-10 RIM link FSHR-1 to synaptic vesicle release further downstream. Future investigations will test proposed G protein pathway components in a cell type-specific manner.
Investigation of the FSHR-1 Receptor and its Downstream Pathway Components in Neuromuscular Signaling
Indianapolis, IN
G protein-coupled receptors (GPCRs) regulate diverse processes in cells ranging from heart cells to neurons. FSHR-1 is a conserved GPCR that controls reproductive processes in metazoans, but is also expressed in nervous systems, such as that of Caenorhabditis elegans, Behavioral data indicate that FSHR-1 regulates signaling at the C. elegans neuromuscular junction (NMJ) where a balance of acetylcholine (ACh) and GABA signaling controls muscle contraction. Loss-of-function (lf) C. elegans mutants in fshr-1 exhibit reduced muscle contraction, which is rescued by re-expression of fshr-1 in either neuron type. However, the pathways 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 to control neuromuscular signaling. We hypothesized that in C. elegans GABA and ACh neurons, FSHR-1 promotes muscle contraction using the GSA-1/ACY-1/PKA pathway to regulate synaptic vesicle release. We used paralysis induced by aldicarb, an acetylcholinesterase inhibitor, to measure neuromuscular signaling in worms with mutations in suspected FSHR-1 pathway components. Worms with gain-of-function (gf) mutations in gsa-1, acy-1, or pka paralyzed faster on aldicarb than wild type controls. Worms with fshr-1(lf) and gsa-1(gf) or acy-1(gf) had paralysis rates comparable to acy-1(gf) or gsa-1(gf) single mutants, suggesting PKA, ACY-1, and GSA-1 influence neuromuscular signaling downstream of FSHR-1. Ongoing experiments are testing whether the transcription factor CREB or the active zone protein UNC-10 RIM link FSHR-1 to synaptic vesicle release further downstream. Future investigations will test proposed G protein pathway components in a cell type-specific manner.