Author Type

Graduate Student

Date of Award

2012

Document Type

Thesis

Publication Status

Version of Record

Submission Date

October 2026

Abstract

Huntington's disease (HD) is caused by an expanded plyglutamine repeat in the huntingtin protein. In this study, I focused on the effect of the mutant huntingtin protein (mhtt) on the subcellular localization of glutamic acid decarboxylase (GAD), the enzyme responsible for synthesizing gama-aminobutyric acid (GABA). Subcellular distribution of GAD65 is significantly altered in two neuronal cell lines that express either the N-terminus or full length mhtt. GAD65 is predominantly associated with the Golgi membrane in cells expressing normal huntingtin (Htt). However, it diffuses in the cytosol of cells expressing mhtt. Palmitoylation of GAD65 is required for GAD65 trafficking, and I demonstrated the palmitoylation of GAD65 is reduced in the HD model. Overexpression of huntingtin-interacting protein 14 (HIP14), the enzyme that palmitoylates GAD65, rescues GAD65 palmitoylation and vesicle-associated trafficking. This data suggests that impairment of GAD65 palmitoylation by mhtt may alter its localization and lead to altered inhibitory neurotransmission in HD.

Extent

x, 39 p. : ill. (some col.)

Comments

by Daniel Rush.|Thesis (M.S.)--Florida Atlantic University, 2012.|Includes bibliography.|Electronic reproduction. Boca Raton, Fla., 2012. Mode of access: World Wide Web.|by Daniel Rush.

Identifier

FADT3352831

Format

pdf

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