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Title Identification of PDLIM7 as a Nedd4-1 Substrate in the Regulation of Skeletal Muscle Mass
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Publication Date
Date Available
Degree Level masters
University/Publisher University of Toronto
Abstract

Skeletal muscle atrophy occurs both as a natural consequence of muscle disuse and aging, and as a pathophysiological response to acute and chronic disease. The ubiquitin proteasome system is the predominant proteolytic machinery responsible for atrophy of skeletal muscle and Nedd4-1 is one of a series of E3 ubiquitin ligases known to mediate inactivity-induced muscle wasting. Muscle substrates of Nedd4-1, and mechanisms by which Nedd4-1 regulates muscle mass, are poorly understood. In the present study, I identified PDLIM7 as a novel target of Nedd4- 1 in skeletal muscle. Nedd4-1 expression in muscle atrophied by denervation is coincident with a decrease in PDLIM7, and PDLIM7 protein levels are stabilized in denervated muscle of Nedd4-1 knockout mice. These results identify PDLIM7 as a bona fide skeletal muscle substrate of Nedd4-1 and suggest that this interaction may underlie the progression of skeletal muscle atrophy, offering a potential therapeutic target to attenuate its onset.

M.Sc.

Subjects/Keywords 0307
Contributors Batt, Jane; Medical Science
Country of Publication ca
Record ID handle:1807/74583
Repository toronto-thes
Date Retrieved
Date Indexed 2019-06-26

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