MuRF1 is a muscle fiber-type II associated factor and together with MuRF2 regulates type-II fiber trophicity and maintenance

Anselmo S. Moriscot, Igor L. Baptista, Julius Bogomolovas, Christian Witt, Stephanie Hirner, Hendrikus "Henk" Granzier, Siegfried Labeit

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

MuRF1 is a member of the RBCC (RING, B-box, coiled-coil) superfamily that has been proposed to act as an atrogin during muscle wasting. Here, we show that MuRF1 is preferentially induced in type-II muscle fibers after denervation. Fourteen days after denervation, MuRF1 protein was further elevated but remained preferentially expressed in type-II muscle fibers. Consistent with a fiber-type dependent function of MuRF1, the tibialis anterior muscle (rich in type-II muscle fibers) was considerably more protected in MuRF1-KO mice from muscle wasting when compared to soleus muscle with mixed fiber-types. We also determined fiber-type distributions in MuRF1/MuRF2 double-deficient KO (dKO) mice, because MuRF2 is a close homolog of MuRF1. MuRF1/MuRF2 dKO mice showed a profound loss of type-II fibers in soleus muscle. As a potential mechanism we identified the interaction of MuRF1/MuRF2 with myozenin-1, a calcineurin/NFAT regulator and a factor required for maintenance of type-II muscle fibers. MuRF1/MuRF2 dKO mice had lost myozenin-1 expression in tibialis anterior muscle, implicating MuRF1/MuRF2 as regulators of the calcineurin/NFAT pathway. In summary, our data suggest that expression of MuRF1 is required for remodeling of type-II fibers under pathophysiological stress states, whereas MuRF1 and MuRF2 together are required for maintenance of type-II fibers, possibly via the regulation of myozenin-1.

Original languageEnglish (US)
Pages (from-to)344-353
Number of pages10
JournalJournal of Structural Biology
Volume170
Issue number2
DOIs
StatePublished - May 2010

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Fast-Twitch Muscle Fibers
Maintenance
Muscles
Calcineurin
Denervation
Skeletal Muscle
Proteins

Keywords

  • MuRF1
  • Muscle atrophy
  • Muscle fiber types
  • Myozenin-1/calsarcin-2

ASJC Scopus subject areas

  • Structural Biology

Cite this

MuRF1 is a muscle fiber-type II associated factor and together with MuRF2 regulates type-II fiber trophicity and maintenance. / Moriscot, Anselmo S.; Baptista, Igor L.; Bogomolovas, Julius; Witt, Christian; Hirner, Stephanie; Granzier, Hendrikus "Henk"; Labeit, Siegfried.

In: Journal of Structural Biology, Vol. 170, No. 2, 05.2010, p. 344-353.

Research output: Contribution to journalArticle

Moriscot, Anselmo S. ; Baptista, Igor L. ; Bogomolovas, Julius ; Witt, Christian ; Hirner, Stephanie ; Granzier, Hendrikus "Henk" ; Labeit, Siegfried. / MuRF1 is a muscle fiber-type II associated factor and together with MuRF2 regulates type-II fiber trophicity and maintenance. In: Journal of Structural Biology. 2010 ; Vol. 170, No. 2. pp. 344-353.
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