Build it up-Tear it down: Protein quality control in the cardiac sarcomere

Monte S. Willis, Jonathan C. Schisler, Andrea L. Portbury, Cam Patterson

Research output: Contribution to journalReview article

102 Scopus citations

Abstract

The assembly and maintenance of the cardiac sarcomere, which contains the basic contractile components of actin and myosin, are essential for cardiac function. While often described as a static structure, the sarcomere is actually dynamic and undergoes constant turnover, allowing it to adapt to physiological changes while still maintaining function. A host of new factors have been identified that play a role in the regulation of protein quality control in the sarcomere, including chaperones that mediate the assembly of sarcomere components and ubiquitin ligases that control their specific degradation. There is clear evidence of sarcomere disorganization in animal models lacking muscle-specific chaperone proteins, illustrating the importance of these molecules in sarcomere structure and function. Although ubiquitin ligases have been found within the sarcomere structure itself, the role of the ubiquitin proteasome system in cardiac sarcomere regulation, and the factors that control its activity, are only just now being elucidated. The number of ubiquitin ligases identified with specificity for sarcomere proteins, each with distinct target substrates, is growing, allowing for tight regulation of this system. In this review, we highlight the dynamic interplay between sarcomere-specific chaperones and ubiquitin-dependent degradation of sarcomere proteins that is necessary in order to maintain structure and function of the cardiac sarcomere.

Original languageEnglish (US)
Pages (from-to)439-448
Number of pages10
JournalCardiovascular research
Volume81
Issue number3
DOIs
StatePublished - Feb 1 2009
Externally publishedYes

Keywords

  • Atrogin-1
  • C-terminal of Hsp70 interacting protein
  • Chaperones
  • GimC
  • MAFbx
  • MDM2
  • Muscle ring finger
  • Proteasome
  • Protein quality control
  • TriC
  • UNC-45
  • UPD-2
  • Ubiquitin
  • Ubiquitin ligase
  • αB-crystallin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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