000000673 001__ 673
000000673 005__ 20260225152244.0
000000673 0247_ $$2DOI$$a10.6083/M4WW7FND
000000673 037__ $$aETD
000000673 245__ $$aThe physiological function and pathogenic role of drosophila protein Swiss cheese
000000673 260__ $$bOregon Health and Science University
000000673 269__ $$a2010
000000673 336__ $$aDissertation
000000673 502__ $$bPh.D.
000000673 502__ $$gNeuroscience
000000673 520__ $$aThis dissertation investigates the physiological role of the Drosophila protein Swiss Cheese (SWS) and its involvement in pesticide‑induced neuropathy. First, a novel function for SWS is identified: regulating the kinase PKA‑C3 by binding it at the membrane and maintaining it in an inactive state. In sws¹ mutants, loss of this regulation leads to overactive PKA‑C3 and neurodegeneration. The work also shows that organophosphate exposure reduces kinase activity, likely by altering SWS and preventing activation of PKA‑C3, and that elevated SWS levels increase organophosphate toxicity. Preliminary data indicate that constitutively active PKA‑C3 or disrupted SWS binding promotes vacuole formation in the brain. Together, these findings demonstrate that SWS and PKA‑C3 interact to maintain neuronal integrity and that disruption of this regulatory system contributes to neurodegenerative disease.
000000673 540__ $$fCC BY
000000673 542__ $$fIn copyright - single owner
000000673 650__ $$aDrosophila Proteins$$033672
000000673 650__ $$aProteins$$024763
000000673 650__ $$aEsters$$018650
000000673 650__ $$aNerve Degeneration$$022797
000000673 650__ $$aNervous System$$022807
000000673 650__ $$aPesticides$$023885
000000673 650__ $$aDisease Models, Animal$$017932
000000673 650__ $$aOrganophosphates$$024056
000000673 6531_ $$aphosphoric acid esters
000000673 691__ $$aSchool of Medicine$$041369
000000673 692__ $$aVollum Institute$$041509
000000673 7001_ $$aWentzell, Jill$$uOregon Health and Science University$$041354
000000673 7201_ $$aKretzschmar, Doris$$uOregon Health and Science University$$041354$$7Personal$$eMentor
000000673 8564_ $$9de82ce97-a5a5-4909-957c-ceccb0ecdade$$s3716282$$uhttps://digitalcollections.ohsu.edu/record/673/files/674_etd.pdf$$ePublic$$2268c40f9382b8757faf400b217437e7f$$31
000000673 905__ $$a/rest/prod/q8/11/kj/62/q811kj62r
000000673 909CO $$ooai:digitalcollections.ohsu.edu:673$$pstudent-work
000000673 956__ $$aGet Accessible Copy$$uhttps://ohsu.libwizard.com/f/requestaccessibledocument
000000673 980__ $$aTheses and Dissertations