Undergraduate Honors Theses

Thesis Defended

Spring 2013

Document Type

Thesis

Department

Molecular, Cellular, & Developmental Biology

First Advisor

Dr. Greg Odorizzi

Abstract

Frontotemporal dementia (FTD) represents a crippling new neurodegenerative disease for scientific investigation. Marked by characteristic frontal and temporal lobar cortical atrophy, FTD results in the progressive deterioration of social and behavioral capabilities. FTD exhibits an autosomal dominant inheritance pattern, and is the second most common form of presenile dementia behind Alzheimer's disease. One subtype of the neuropathy, designated as frontotemporal dementia linked to chromosome 3 (FTD3), has been traced to a single truncating mutation in the human protein CHMP2B. Fortunately, S. cerevisiae ortholog Vps2 shares conserved function with CHMP2B, and functions analogously as a constituent of the ESCRTmediated endocytic pathway, necessary for protein trafficking and degradation within the cell. In order to investigate the mechanism and genetics behind FTD3 pathology, a corresponding mutation has been created in yeast, and a variety of assays examining its function have been conducted. This projects details the mutation’s potential effects on autophagy, as well as the critical polymerization of ESCRT-III component Snf7. Ultimately, this exposition suggests that autophagy is not affected by the FTD3 mutation. Additionally, heterozygous expression of mutated Vps2 does not appear to cause aberrant Snf7 polymerization, while haploid expression does seem to affect the process. Finally, proposed future experiments should continue to help resolve the mechanism behind frontotemporal dementia linked to chromosome 3.

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