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INVESTIGATING THE ROLE OF PEN-2 IN REGULATING MATURE Y-SECRETASE PROTEOLYTIC ACTIVITY AND ITS IMPACT ON CELL SURVIVABILITY IN DROSOPHILA MELANOGASTER
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INVESTIGATING THE ROLE OF PEN-2 IN REGULATING MATURE Y-SECRETASE PROTEOLYTIC ACTIVITY AND ITS IMPACT ON CELL SURVIVABILITY IN DROSOPHILA MELANOGASTER

Joel Michael Brown
University of West Florida
Master of Science (MS), University of West Florida
2012

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Abstract

Presenilin enhancer 2 (Pen-2) is one of four components of the a-secretase complex along with Presenilin (Psn), Aph-1, and Nicastrin (Nct). Among these four, Psn is the catalytic subunit, whose maturation depends on Aph-1, Nct, and Pen-2 to give rise to a Psn-NTF/CTF heterodimer during a-secretase assembly. a-Secretase is an important protease responsible for processing several type I transmembrane proteins such as Amyloid Precursor Protein and Notch. Abnormal a-secretase activity increases APP-derived AB aggregates in Alzheimer's disease patients. In this study, mosaic analysis and RNA interference were used to investigate the role of Pen-2 in a-secretase by looking at clones on the Drosophila melanogaster larval wing disc. The RNAi was performed in flies which transgenically expressed various Presenilin forms that either require or circumvent the need for Pen-2 activation. In this environment, "artificially matured" a-secretase activity was assayed in the absence of Pen-2 by observing the a-secretase mediated, Notch-dependent localization of cut expression on the wing disc. Mutant clone sizes were also analyzed for potential cell death. In addition to its role in maturation, results suggest that Pen-2 is not required for y-secretase activity post-maturation and does not appear to affect cell survivability on the Drosophila wing disc.
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