Date

November 2010

Document Type

Dissertation

Degree Name

Ph.D.

Institution

Oregon Health & Science University

Abstract

This dissertation looks at the physiological role of the Drosophila protein Swiss Cheese (SWS) and the involvement of Swiss Cheese in the development of a neuropathy associated with pesticide exposure. A brief introductory chapter presents background on the discovery of the SWS protein and the Pesticide induced neuropathy. Chapter 2 describes a new physiological role for SWS as a regulator of a highly conserved kinase, PKA-C3. Evidence is presented that SWS binds this kinase, keeping it membrane bound and inactive. Overactive PKA-C3 in sws[superscript 1] flies is thought to play a role in the degenerative phenotype associated with these mutants, suggesting that activity of PKA-C3 is tightly regulated in vivo. Chapter 3 presents evidence that exposure to Organophosphates (OPs) decreases kinase activity and we propose this is due to action of OPs on SWS, which then prevents SWS from releasing and activating PKA-C3. We show that increased levels of SWS protein increase the toxicity of OPs

Identifier

doi:10.6083/M4WW7FND

Division

Neuroscience Graduate Program

School

School of Medicine

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