Deficiency in APOBEC2 leads to a shift in muscle fiber type, diminished body mass, and myopathy

Yusuke Sato, Hans Christian Probst, Ryuichi Tatsumi, Yoshihide Ikeuchi, Michael S. Neuberger, Cristina Rada

Research output: Contribution to journalArticlepeer-review

71 Citations (Scopus)

Abstract

The apoB RNA-editing enzyme, catalytic polypeptide-like (APOBEC) family of proteins includes APOBEC1, APOBEC3, and activation-induced deaminase, all of which are zincdependent cytidine deaminases active on polynucleotides and involved in RNA editing or DNA mutation. In contrast, the biochemical and physiological functions of APOBEC2, a musclespecific member of the family, are unknown, although it has been speculated, like APOBEC1, to be an RNA-editing enzyme. Here, we show that, although expressed widely in striated muscle (with levels peaking late during myoblast differentiation), APOBEC2 is preferentially associated with slow-twitch muscle, with its abundance being considerably greater in soleus compared with gastrocnemius muscle and, within soleus muscle, in slow as opposed to fast muscle fibers. Its abundance also decreases following muscle denervation. We further show that APOBEC2-deficient mice harbor a markedly increased ratio of slow to fast fibers in soleus muscle and exhibit an ∼15-20% reduction in body mass from birth onwards, with elderly mutant animals revealing clear histological evidence of a mild myopathy. Thus, APOBEC2 is essential for normal muscle development and maintenance of fiber-type ratios; although its molecular function remains to be identified, biochemical analyses do not especially argue for any role in RNA editing.

Original languageEnglish
Pages (from-to)7111-7118
Number of pages8
JournalJournal of Biological Chemistry
Volume285
Issue number10
DOIs
Publication statusPublished - Mar 5 2010

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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