Biology

Investigation of the FSHR-1 Receptor as a Potential Substrate of the Anaphase Promoting Complex at the C. elegans Neuromuscular Junction

Document Type

Oral Presentation

Location

Indianapolis, IN

Start Date

13-4-2018 10:30 AM

End Date

13-4-2018 11:45 AM

Description

Healthy nervous system function requires a balance of excitatory and inhibitory (E:I) neuronal signaling. This E:I balance relies upon the ubiquitin system, a process that regulates many proteins within cells through enzymatic tagging with ubiquitin polypeptides to affect their activity and abundance. Proper function of ubiquitin enzymes like the Anaphase Promoting Complex (APC), a ubiquitin ligase, and its substrates is needed for regulation of E:I balance. E:I imbalances occur in many neurological diseases, so a better understanding of the APC and its substrates may lead to improved treatments for diseases like Parkinson's and epilepsy. Our previous data showed the APC acts in inhibitory C. elegans GABA neurons to promote GABA neurotransmitter release, but APC substrates relevant for this effect are unknown. Follicle Stimulating Hormone Receptor 1 (FSHR-1) is a possible APC substrate. FSHR-1 possesses recognition sequences for APC interaction, and both fshr-1 and fshr-1;apc loss of function mutants exhibit decreased muscle contraction, indicating FSHR-1 acts after the APC to control signaling. I am testing the hypothesis that FSHR-1 is an APC substrate by generating worms expressing fluorescently tagged FSHR-1 and quantitatively measuring changes in neuronal FSHR-1::GFP concentrations when the APC is non-functional. Current work is also focused on determining the cell types in which FSHR-1 is endogenously expressed. If FSHR-1 is a target of the APC enzyme, I expect higher FSHR-1::GFP concentrations in APC loss of function worms and for FSHR-1 to be expressed in neuron classes in which the APC is expressed.

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Apr 13th, 10:30 AM Apr 13th, 11:45 AM

Investigation of the FSHR-1 Receptor as a Potential Substrate of the Anaphase Promoting Complex at the C. elegans Neuromuscular Junction

Indianapolis, IN

Healthy nervous system function requires a balance of excitatory and inhibitory (E:I) neuronal signaling. This E:I balance relies upon the ubiquitin system, a process that regulates many proteins within cells through enzymatic tagging with ubiquitin polypeptides to affect their activity and abundance. Proper function of ubiquitin enzymes like the Anaphase Promoting Complex (APC), a ubiquitin ligase, and its substrates is needed for regulation of E:I balance. E:I imbalances occur in many neurological diseases, so a better understanding of the APC and its substrates may lead to improved treatments for diseases like Parkinson's and epilepsy. Our previous data showed the APC acts in inhibitory C. elegans GABA neurons to promote GABA neurotransmitter release, but APC substrates relevant for this effect are unknown. Follicle Stimulating Hormone Receptor 1 (FSHR-1) is a possible APC substrate. FSHR-1 possesses recognition sequences for APC interaction, and both fshr-1 and fshr-1;apc loss of function mutants exhibit decreased muscle contraction, indicating FSHR-1 acts after the APC to control signaling. I am testing the hypothesis that FSHR-1 is an APC substrate by generating worms expressing fluorescently tagged FSHR-1 and quantitatively measuring changes in neuronal FSHR-1::GFP concentrations when the APC is non-functional. Current work is also focused on determining the cell types in which FSHR-1 is endogenously expressed. If FSHR-1 is a target of the APC enzyme, I expect higher FSHR-1::GFP concentrations in APC loss of function worms and for FSHR-1 to be expressed in neuron classes in which the APC is expressed.