Cytoplasmic Gamma-actin Contributes to a Compensatory Remodeling Response in Dystrophin-deficient Muscle

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2006 Mar 28

PMID 16565216

Citations 46

Authors

Laurin M Hanft

Inna N Rybakova

Jitandrakumar R Patel

Jill A Rafael-Fortney

James M Ervasti

Affiliations

Soon will be listed here.

Abstract

Dystrophin mechanically links the costameric cytoskeleton and sarcolemma, yet dystrophin-deficient muscle exhibits abnormalities in cell signaling, gene expression, and contractile function that are not clearly understood. We generated new antibodies specific for cytoplasmic gamma-actin and confirmed that gamma-actin most predominantly localized to the sarcolemma and in a faint reticular lattice within normal muscle cells. However, we observed that gamma-actin levels were increased 10-fold at the sarcolemma and within the cytoplasm of striated muscle cells from dystrophin-deficient mdx mice. Transgenic overexpression of the dystrophin homologue utrophin, or functional dystrophin constructs in mdx muscle, restored gamma-actin to normal levels, whereas gamma-actin remained elevated in mdx muscle expressing nonfunctional dystrophin constructs. We conclude that increased cytoplasmic gamma-actin in dystrophin-deficient muscle may be a compensatory response to fortify the weakened costameric lattice through recruitment of parallel mechanical linkages. However, the presence of excessive myoplasmic gamma-actin may also contribute to altered cell signaling or gene expression in dystrophin-deficient muscle.

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