The physiological function and pathogenic role of drosophila protein Swiss cheese

This 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.