Preparing your results

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

During muscle atrophy, thick, but not thin, filament components are degraded by MuRF1-dependent ubiquitylation.

Loss of myofibrillar proteins is a hallmark of atrophying muscle. Expression of muscle RING-finger 1 (MuRF1), a ubiquitin ligase, is markedly induced during atrophy, and MuRF1 deletion attenuates muscle wasting. We generated mice expressing a Ring-deletion mutant MuRF1, which binds but cannot ubiquitylate substrates. Mass spectrometry of the bound proteins in denervated muscle identified many myofibrillar components. Upon denervation or fasting, atrophying muscles show a loss of myosin-binding protein C (MyBP-C) and myosin light chains 1 and 2 (MyLC1 and MyLC2) from the myofibril, before any measurable decrease in myosin heavy chain (MyHC). Their selective loss requires MuRF1. MyHC is protected from ubiquitylation in myofibrils by associated proteins, but eventually undergoes MuRF1-dependent degradation. In contrast, MuRF1 ubiquitylates MyBP-C, MyLC1, and MyLC2, even in myofibrils. Because these proteins stabilize the thick filament, their selective ubiquitylation may facilitate thick filament disassembly. However, the thin filament components decreased by a mechanism not requiring MuRF1.

Pubmed ID: 19506036


  • Cohen S
  • Brault JJ
  • Gygi SP
  • Glass DJ
  • Valenzuela DM
  • Gartner C
  • Latres E
  • Goldberg AL


The Journal of cell biology

Publication Data

June 15, 2009

Associated Grants

  • Agency: NIAMS NIH HHS, Id: F32 AR054699
  • Agency: NIAMS NIH HHS, Id: R01 AR055255
  • Agency: NIAMS NIH HHS, Id: R01 AR055255-02

Mesh Terms

  • Actomyosin
  • Animals
  • Carrier Proteins
  • Denervation
  • Fasting
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Muscle Proteins
  • Muscle, Skeletal
  • Muscular Atrophy
  • Myofibrils
  • Myosin Light Chains
  • Protein Binding
  • Ubiquitin
  • Ubiquitin-Protein Ligases
  • Ubiquitination