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dc.contributor.advisorAilion, Michael
dc.contributor.authorColeman, Brantley David
dc.date.accessioned2018-04-24T22:17:37Z
dc.date.available2018-04-24T22:17:37Z
dc.date.submitted2018
dc.identifier.otherColeman_washington_0250E_18378.pdf
dc.identifier.urihttp://hdl.handle.net/1773/41741
dc.descriptionThesis (Ph.D.)--University of Washington, 2018
dc.description.abstractThe heterotrimeric G protein Gq regulates neuronal activity through distinct downstream effector pathways. In addition to the canonical Gq effector phospholipase C beta, the small GTPase Rho was recently identified as a conserved effector of Gq. To identify additional molecules important for Gq signaling in neurons, we performed a forward genetic screen in the nematode Caenorhabditis elegans for suppressors of the hyperactivity and exaggerated waveform of an activated Gq mutant. We isolated two mutations affecting the MAP kinase scaffold protein KSR-1 and found that KSR-1 modulates locomotion downstream of or in parallel to the Gq-Rho pathway. Through epistasis experiments, I found that the core ERK MAPK cascade is required for Gq-Rho regulation of locomotion, but that the canonical ERK activator LET-60/Ras may not be required. Through neuron-specific rescue experiments, I found that the ERK pathway functions in acetylcholine neurons to control Gq-dependent locomotion. Additionally, expression of activated LIN-45/Raf in acetylcholine neurons is sufficient to cause an exaggerated waveform phenotype and hypersensitivity to the acetylcholinesterase inhibitor aldicarb, similar to an activated Gq mutant. Taken together, our results suggest that the ERK MAPK pathway modulates the output of Gq-Rho signaling to control locomotion behavior in C. elegans.
dc.format.mimetypeapplication/pdf
dc.language.isoen_US
dc.rightsnone
dc.subjectelegans
dc.subjectERK
dc.subjectGq
dc.subjectMAPK
dc.subjectRho
dc.subjectGenetics
dc.subjectMolecular biology
dc.subject.otherBiological chemistry
dc.titleThe ERK MAPK pathway modulates Gq-dependent locomotion in Caenorhabditis elegans
dc.typeThesis
dc.embargo.termsOpen Access


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