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Thesis
DETERMINING PRESENILIN'S ROLE IN CELL DEATH IN DROSOPHILA MELANOGASTER
University of West Florida
Master of Science (MS), University of West Florida
2018
Abstract
Many cellular mechanisms essential to life are evolutionarily conserved among animal species; Presenilin is one of such examples. Presenilin is a 9-pass transmembrane protein that functions as a subunit of the vital enzyme y-secretase, which is a fundamental mediator for cell-cell communication in animal development. Presenilin has been found to act both dependently with, and independent from y-secretase activity. Mutations in Presenilin are linked to the neurodegenerative pathology of Alzheimer's disease (AD). Brain atrophy, caused by neuronal cell death, is a prominent pathological trait of AD. The mechanisms in which this cell death occurs remain largely undetermined. This study focuses on determining the role of Presenilin (Psn) on cell death in Drosophila melanogaster. Previous studies have suggested that Psn has some pro-apoptotic characteristics and that Psn may interact with members of the bcl-2 gene family, a family of genes involved in mitochondrial mediated cell death pathways. Drosophila is an ideal model organism to study intrinsic cell death because there are only two Bcl-2 family proteins, the pro-survival protein, Buffy, and pro-cell death protein Debcl. The tumor suppressor transcription factor Rbf1 has been shown to act in the Bcl-2 cell death pathway as well by suppressing buffy transcription. I hypothesize that Psn promotes cell death through Debcl-mediated cell death pathway. I also hypothesize that the majority of Psn usually undergoes endoproteolysis and participates in the assembly of g-secretase complex (major route) to promote cell proliferation but it can also interact with Bcl-2 family proteins at the mitochondrion to promote cell death (minor route) independently of y-secretase activity. To test this hypothesis, I examine whether overexpressing debcl or rbf1 can still induce cell death during Drosophila wing development, in the context of either the presence or absence of Psn. In this study, when debcl is overexpressed while simultaneously knocking down psn expression, the cell death phenotype seen when overexpressing debcl alone is no longer observed. However, when overexpressing debcl in the knock-down presence of the g-secretase dependent protein nicastrin (nct), cell death is still observed. These results suggest that Psn promotes Debcl-mediated cell death through genetic interaction with Debcl independent of g-secretase activity.
Details
- Title
- DETERMINING PRESENILIN'S ROLE IN CELL DEATH IN DROSOPHILA MELANOGASTER
- Resource Type
- Thesis
- Publisher
- University of West Florida
- Format
- text
- Copyright
- http://rightsstatements.org/vocab/InC-EDU/1.0/
- Identifiers
- 99380090836706600
- Academic Unit
- Biology
- Language
- English
- Awarding Institution
- University of West Florida; Master of Science (MS)
- Theses and Dissertations
- Master of Science (MS), University of West Florida