Developmental regulation of MURF E3 ubiquitin ligases in skeletal muscle

Sue Perera, Baljinder Mankoo, Mathias Gautel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

The striated muscle-specific tripartite motif (TRIM) proteins TRIM63/MURF1, TRIM55/MURF2 and TRIM54/MURF3 can function as E3 ubiquitin ligases in ubiquitin-mediated muscle protein turnover. Despite the well-characterised role of MURF1 in skeletal muscle atrophy, the dynamics of MURF isogene expression in the development and early postnatal adaptation of skeletal muscle is unknown. Here, we show that MURF2 is the isogene most highly expressed in embryonic skeletal muscle at E15.5, with the 50 kDa A isoform predominantly expressed. MURF1 and MURF3 are upregulated only postnatally. Knockdown of MURF2 p50A by isoform-specific siRNA results in delayed myogenic differentiation and myotube formation in vitro, with perturbation of the stable, glutamylated microtubule population. This underscores that MURF2 plays an important role in the earliest stages of skeletal muscle differentiation and myofibrillogenesis. During further development, there is a shift towards the 60 kDa A isoform, which dominates postnatally. Analysis of the fibre-type expression shows that MURF2 A isoforms are predominantly slow-fibre associated, whilst MURF1 is largely excluded from these fibres, and MURF3 is ubiquitously distributed in both type I and II fibres.

Original languageEnglish
Article numberN/A
Pages (from-to)107-122
Number of pages16
JournalJournal of Muscle Research and Cell Motility
Volume33
Issue number2
DOIs
Publication statusPublished - Jun 2012

Keywords

  • MURF
  • p62
  • SQSTM1
  • NBR1
  • Myofibrils
  • Microtubules
  • Skeletal muscle development
  • Fibre-type differentiation
  • Slow fibres
  • SERUM RESPONSE FACTOR
  • MYOSIN HEAVY-CHAINS
  • RING-FINGER PROTEIN
  • MYOGENIC DIFFERENTIATION
  • SIGNALING PATHWAYS
  • KINASE DOMAIN
  • FIBER TYPES
  • AUTOPHAGY
  • ATROPHY
  • MICROTUBULE

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