Posttranslational modifications of cardiac troponin T: An overview

• Published in: Journal of molecular and cellular cardiology Vol. 63; pp. 47 - 56
• Main Authors: Streng, Alexander S., de Boer, Douwe, van der Velden, Jolanda, van Dieijen-Visser, Marja P., Wodzig, Will K.W.H.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2013
• Subjects: Animals; Cardiac physiology; Cardiac troponin T; Cardiovascular; Fragmentation; Humans; Myocardium - metabolism; Phosphorylation; Protein Processing, Post-Translational; Proteolysis; Troponin T - chemistry; Troponin T - metabolism; ESRD; PAK1/3; Phosphorylation; CaMK II; RV; GFC; ASK1; MS; PTM; ROCK-II; LV; cTnT/I/C; Fragmentation; PP1; Cardiac physiology; PKA/C/D; Pi; Tm; AMI; HF; Cardiac troponin T; left ventricle; PP2A, protein phosphatase 1, 2A; posttranslational modification; rho-A-dependent protein kinase; apoptosis signal-regulating kinase 1; tropomyosin; P i; mass spectrometry; inorganic phosphate; Ca 2 + /calmodulin-dependent protein kinase II; p21 activated kinase 1, 3; heart failure; cardiac troponin T, I, C; end-stage renal disease; protein kinase A, C, D; gel filtration chromatography; right ventricle; acute myocardial infarction; P(i); Ca(2+)/calmodulin-dependent protein kinase II
• ISSN: 0022-2828; 1095-8584; 1095-8584
• DOI: 10.1016/j.yjmcc.2013.07.004

Cardiac troponin (cTn) is an important sarcomeric protein complex situated on the thin filament and is involved in the regulation of cardiac muscle contraction. This regulation is primarily controlled by Ca2+ binding to troponin C and in addition fine-tuned by the posttranslational modification of cTnI and cTnT. The vast majority of cTnT modifications involve the phosphorylation by protein kinase C (PKC) or other kinases and the N-terminal cleavage by caspase and calpain. In vitro studies employing reconstituted detergent-skinned fiber bundles and cell culture generally show a detrimental effect of cTnT phosphorylation on muscle contraction, which is backed by some in vivo studies finding increased cTnT phosphorylation in heart failure, but contradicted by others. In addition, N-terminal cleavage of cTnT is thought to be another factor influencing cardiac contraction. Time-dependent degradation of cTnT has been observed in human serum upon myocardial infarction. These molecular changes might influence the immunoreactivity of cTnT in the clinical immunoassay and have consequences for the clinical interpretations of these measurements. No consensus has yet been reached on the occurrence and extent of these observations and their underlying processes are subject of intense scientific debate. This review will focus on discussing these modifications, their implications on physiology and disease and summarizes the complex interplays of different enzymes on the molecular forms of cTnT and their associated effects. •This review describes posttranslational modifications of cardiac troponin T (cTnT).•cTnT phosphorylation has a detrimental effect on cardiomyocyte contractility.•cTnT phosphorylation is altered in disease.•N-terminal cleavage of cTnT may also influence contractility.•These modifications can influence the immunoreactivity of clinical troponin assays.