TY - JOUR
T1 - Deficiency in APOBEC2 leads to a shift in muscle fiber type, diminished body mass, and myopathy
AU - Sato, Yusuke
AU - Probst, Hans Christian
AU - Tatsumi, Ryuichi
AU - Ikeuchi, Yoshihide
AU - Neuberger, Michael S.
AU - Rada, Cristina
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/3/5
Y1 - 2010/3/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77951218276&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77951218276&partnerID=8YFLogxK
U2 - 10.1074/jbc.M109.052977
DO - 10.1074/jbc.M109.052977
M3 - Article
C2 - 20022958
AN - SCOPUS:77951218276
VL - 285
SP - 7111
EP - 7118
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 10
ER -