Modulation of thin filament activation by breakdown or isoform switching of thin filament proteins: physiological and pathological implications.
In the heart, the contractile apparatus is adapted to the specific demands of the organ for continuous rhythmic contraction. The specialized contractile properties of heart muscle are attributable to the expression of cardiac-specific isoforms of contractile proteins. This review describes the isoforms of the thin filament proteins actin and tropomyosin and the three troponin subunits found in human heart muscle, how the isoform profiles of these proteins change during development and disease, and the possible functional consequences of these changes. During development of the heart, there is a distinctive switch of isoform expression at or shortly after birth; however, during adult life, thin filament protein isoform composition seems to be stable despite protein turnover rates of 3 to 10 days. The pattern of isoforms of actin, tropomyosin, troponin I, troponin C, and troponin T is not affected by aging or heart disease (ischemia and dilated cardiomyopathy). The evidence for proteolysis of thin filament proteins in situ during ischemia and stunning is evaluated, and it is concluded that C-terminal cleavage of troponin I is a feature of irreversibly injured myocardium but may not play a role in reversible stunning.
Marston
Steven B
SB
Imperial College London, National Heart and Lung Institute, Dovehouse St, London SW3 6LY, UK. S.Marston@imperial.ac.uk
Redwood
Charles S
CS
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015870:Gene Expression; D006801:Humans; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014335:Tropomyosin / Q000235:genetics / Q000378:metabolism; D019209:Troponin C / Q000235:genetics / Q000378:metabolism; D019210:Troponin I / Q000235:genetics / Q000378:metabolism; D020107:Troponin T / Q000235:genetics / Q000378:metabolism
D000199:Actins; D009124:Muscle Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D014335:Tropomyosin; D019209:Troponin C; D019210:Troponin I; D020107:Troponin T