Build it up-Tear it down: protein quality control in the cardiac sarcomere.
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.
Willis
Monte S
MS
Carolina Cardiovascular Biology Center, University of North Carolina, 8200 Medical Biomolecular Research Bldg, 103 Mason Farm Road, Chapel Hill, NC 27599-7126, USA.
Schisler
Jonathan C
JC
Portbury
Andrea L
AL
Patterson
Cam
C
D000199:Actins / Q000378:metabolism; D000222:Adaptation, Physiological; D000818:Animals; D001343:Autophagy; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D009202:Cardiomyopathies / Q000378:metabolism* / Q000503:physiopathology; D003893:Desmin / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D009119:Muscle Contraction; D009124:Muscle Proteins / Q000097:blood*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012518:Sarcomeres / Q000201:enzymology / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D038203:alpha-Crystallin B Chain / Q000378:metabolism
D000199:Actins; D029742:Caenorhabditis elegans Proteins; D003893:Desmin; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D009124:Muscle Proteins; D025801:Ubiquitin; D038203:alpha-Crystallin B Chain; C107348:unc-45 protein, C elegans; D044767:Ubiquitin-Protein Ligases; D002154:Calpain; D046988:Proteasome Endopeptidase Complex; D009218:Myosins