Context-dependent functional substitution of α-skeletal actin by γ-cytoplasmic actin

Michele A. Jaeger, Kevin J. Sonnemann, Daniel P. Fitzsimons, Kurt W. Prins, James M. Ervasti

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

We generated transgenic mice that overexpressed γ-cyto actin 2000-fold above wild-type levels in skeletal muscle. γ- cyto actin comprised 40% of total actin in transgenic skeletal muscle, with a concomitant 40% decrease in •-actin. Surprisingly, transgenic muscle was histologically and ultrastructurally identical to wild-type muscle despite near-stoichiometric incorporation of γ- cyto actin into sarcomeric thin filaments. Furthermore, several parameters of muscle physiological performance in the transgenic animals were not different from wild type. Given these surprising results, we tested whether overexpression of γ-cyto actin could rescue the early postnatal lethality in α-sk actin-null mice (Acta1-/-). By quantitative Western blot analysis, we found total actin levels were decreased by 35% in Acta1-/- muscle. Although transgenic overexpression of γ-cyto actin on the Acta1-/- background restored total actin levels to wild type, resulting in thin filaments composed of 60% γ-cyto actin and a 40% mixture of cardiac and vascular actin, the life span of transgenic Acta1-/- mice was not extended. These results indicate that sarcomeric thin filaments can accommodate substantial incorporation of γ-cyto actin without functional consequences, yet γ-cyto actin cannot fully substitute for α- sk actin.

Original languageEnglish (US)
Pages (from-to)2205-2214
Number of pages10
JournalFASEB Journal
Volume23
Issue number7
DOIs
StatePublished - Jul 2009

Keywords

  • Isoform substitution
  • Isoforms
  • Myofibril
  • Nemaline myopathy
  • Sarcomere
  • Thin filament

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