Molecular and functional characterization of a novel cardiac-specific human tropomyosin isoform.

Content Provider	Semantic Scholar
Author	Rajan, Sudarsan Jagatheesan, Ganapathy Karam, Chehade N. Alves, Marco Stephan Lofrano Bodi, Ilona Schwartz, Arnold H. Bulcao, Christian F. D'souza, Karen M. Akhter, Shahab A. Boivin, Greg P. Dube, Dipak K. Petrashevskaya, Natalia Herr, Andrew B. Hullin, Roger Liggett, Stephen Bryant Wolska, Beata Małgorzata Solaro, Ross John Wieczorek, David F.
Copyright Year	2010
Abstract	BACKGROUND Tropomyosin (TM), an essential actin-binding protein, is central to the control of calcium-regulated striated muscle contraction. Although TPM1alpha (also called alpha-TM) is the predominant TM isoform in human hearts, the precise TM isoform composition remains unclear. METHODS AND RESULTS In this study, we quantified for the first time the levels of striated muscle TM isoforms in human heart, including a novel isoform called TPM1kappa. By developing a TPM1kappa-specific antibody, we found that the TPM1kappa protein is expressed and incorporated into organized myofibrils in hearts and that its level is increased in human dilated cardiomyopathy and heart failure. To investigate the role of TPM1kappa in sarcomeric function, we generated transgenic mice overexpressing cardiac-specific TPM1kappa. Incorporation of increased levels of TPM1kappa protein in myofilaments leads to dilated cardiomyopathy. Physiological alterations include decreased fractional shortening, systolic and diastolic dysfunction, and decreased myofilament calcium sensitivity with no change in maximum developed tension. Additional biophysical studies demonstrate less structural stability and weaker actin-binding affinity of TPM1kappa compared with TPM1alpha. CONCLUSIONS This functional analysis of TPM1kappa provides a possible mechanism for the consequences of the TM isoform switch observed in dilated cardiomyopathy and heart failure patients.
Starting Page	902
Ending Page	909
Page Count	8
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://circ.ahajournals.org/content/circulationaha/121/3/410.full.pdf?download=true
PubMed reference number	20065163v1
Alternate Webpage(s)	https://doi.org/10.1161/CIRCULATIONAHA.109.889725
DOI	10.1161/circulationaha.109.889725
Journal	Circulation
Volume Number	121
Issue Number	3
Language	English
Access Restriction	Open
Subject Keyword	Affinity Calcium Cardiomyopathies Cardiomyopathy, Dilated Diastole Heart failure Microfilaments Muscle Contraction Muscle, Striated Myofilaments Orphan Nuclear Receptor ROR-gammaT Patients Protein Isoforms Tension Tropomyosin diastolic dysfunction type I interferon receptor
Content Type	Text
Resource Type	Article