The miscommunicative cardiac cell: when good proteins go bad.
Troponin (Tn) is made up of three subunits, troponin T (TnT), troponin I (TnI), and troponin C (TnC). In cardiac muscle, TnI can exist as two isoforms, slow skeletal TnI (ssTnI) or cardiac TnI (cTnI), whereas TnT occurs as multiple isoforms. The predominant form of TnI in fetal cardiac muscle is ssTnI, which is derived from a different gene than cTnI. However, the predominant form of cardiac TnT (cTnT) in fetal muscle is cTnT1, which is derived from the same gene that produces the adult cTnT isoform (cTnT3). Fetal cardiac muscle is more sensitive to Ca(2+) than adult muscle and this may be due in part to the fetal cTnT1 and ssTnI isoforms. cTnT1 and/or ssTnI by themselves cause a significant increase in Ca(2+) sensitivity when compared to cTnT3 and/or cTnI. Mutations in the gene for cTnT can cause hypertrophic cardiomyopathy or dilated cardiomyopathy (DCM). Investigation of DCM mutations in the fetal cTnT1 isoform showed that the cTnT isoform is an important determinant of the effect of the mutation. The TnI isoform also affects the physiological function of the cardiac muscle. The presence of both the fetal TnT isoform, containing a DCM mutation, and ssTnI results in larger changes in Ca(2+) sensitivity than the same DCM mutant in the adult TnT isoform and in the presence of cTnI (when compared to their respective wild-type TnT controls). These recent results suggest that some mutations may have different severities in fetal and adult hearts.
Gomes
Aldrin V
AV
Dept. of Molecular and Cellular Pharmacology, Leonard M. Miller School of Medicine at the University of Miami, 1600 N.W. 10th Avenue, Miami, FL 33136, USA.
Venkatraman
Gayathri
G
Potter
James D
JD
D000328:Adult; D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000503:physiopathology*; D002450:Cell Communication; D005315:Fetal Diseases / Q000235:genetics / Q000503:physiopathology*; D006321:Heart / Q000196:embryology / Q000503:physiopathology*; D006801:Humans; D009154:Mutation; D020033:Protein Isoforms / Q000235:genetics; D020107:Troponin T / Q000235:genetics*
D020033:Protein Isoforms; D020107:Troponin T; D002118:Calcium