Functional Importance of the Carboxyl-terminal Region of Striated Muscle Tropomyosin
| Autor: | Greg P. Boivin, Arnold Schwartz, Susan Vahebi, David F. Wieczorek, R. John Solaro, Ganapathy Jagatheesan, Sudarsan Rajan, Pieter deTombe, Erin Labitzke, George M. Hilliard, Natalia Petrashevskaya |
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| Rok vydání: | 2003 |
| Předmět: |
Myofilament
Recombinant Fusion Proteins Troponin T binding Blood Pressure Mice Transgenic Tropomyosin In Vitro Techniques Biochemistry Sarcomere Mice Troponin T Troponin complex Heart Rate Troponin I medicine Animals Protein Isoforms Electrophoresis Gel Two-Dimensional Muscle Skeletal Molecular Biology Actin Binding Sites Chemistry Isoproterenol Heart Cell Biology Myocardial Contraction Biophysics medicine.symptom Muscle contraction |
| Zdroj: | Journal of Biological Chemistry. 278:23204-23211 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m303073200 |
| Popis: | Striated muscle tropomyosin (TM) interacts with actin and the troponin complex to regulate calcium-mediated muscle contraction. Previous work by our laboratory established that alpha- and beta-TM isoforms elicit physiological differences in sarcomeric performance. Heart myofilaments containing beta-TM exhibit an increased sensitivity to calcium that is associated with a decrease in the rate of relaxation and a prolonged time of relaxation. To address whether the carboxyl-terminal, troponin T binding domain of beta-TM is responsible for these physiological alterations, we exchanged the 27 terminal amino acids of alpha-TM (amino acids 258 -284) for the corresponding region in beta-TM. Hearts of transgenic mice that express this chimeric TM protein exhibit significant decreases in their rates of contraction and relaxation when assessed by ex vivo work-performing cardiac analyses. There are increases in the time to peak pressure and a dramatic increase in end diastolic pressure. In myofilaments, this chimeric protein induces depression of maximum tension and ATPase rate, together with a significant decrease in sensitivity to calcium. Our data are the first to demonstrate that the TM isoform-specific carboxyl terminus is a critical determinant of sarcomere performance and calcium sensitivity in both the whole heart and in isolated myofilaments. |
| Databáze: | OpenAIRE |
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