Searching for the missing link: a role for the actin capping protein in heart failure.
Cardiac Z-discs have historically been classified as passive myocardial elements. Z-discs are positioned at the junction between the cytoskeleton and the myofilaments, providing a physical connection between the sarcomere, nucleus, membrane and sarcoplasmic reticulum. Moreover, numerous molecular messengers congregate at the Z-disc. The combination of physical and chemical signals moving through the Z-disc makes this myocardial element a vital switching station of the heart, and suggests significant regulatory potential. Using the actin capping protein (CapZ) as a representative of the Z-disc, it was found that decreasing CapZ enhances force development and inhibits protein kinase C, a messenger of heart failure. These results indicate the potential for CapZ as a therapeutic target in the management of heart failure. Future research is required to determine the mechanisms by which changes in CapZ impact myocardial function and intracellular signalling, and to develop feasible strategies that can manipulate CapZ in the intact heart.
Pyle
W Glen
WG
Department of Biomedical Sciences, University of Guelph, Guelph, Ontario N1G 2W1, Canada. gpyle@uoguelph.ca
D051344:Actin Capping Proteins; D008841:Actin Cytoskeleton / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D051339:Actin Depolymerizing Factors; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D051347:CapZ Actin Capping Protein; D002316:Cardiotonic Agents / Q000627:therapeutic use; D051345:Destrin; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D008840:Microfilament Proteins / Q000187:drug effects / Q000378:metabolism*; D009124:Muscle Proteins / Q000187:drug effects / Q000378:metabolism*; D011379:Prognosis; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D015398:Signal Transduction
D051344:Actin Capping Proteins; D051339:Actin Depolymerizing Factors; D015415:Biomarkers; C495842:CAPZA1 protein, human; D051347:CapZ Actin Capping Protein; D002316:Cardiotonic Agents; D051345:Destrin; D008840:Microfilament Proteins; D009124:Muscle Proteins; D011493:Protein Kinase C