Details

Autor(en) / Beteiligte

• Jagatheesan, Ganapathy
• Rajan, Sudarsan
• Petrashevskaya, Natalia
• Schwartz, Arnold
• Boivin, Greg
• Vahebi, Susan
• DeTombe, Pieter
• Solaro, R John
• Labitzke, Erin
• Hilliard, George
• Wieczorek, David F

Titel

Functional Importance of the Carboxyl-terminal Region of Striated Muscle Tropomyosin

Ist Teil von

• The Journal of biological chemistry, 2003-06, Vol.278 (25), p.23204-23211

Ort / Verlag

United States: American Society for Biochemistry and Molecular Biology

Erscheinungsjahr

2003

Quelle

MEDLINE

Beschreibungen/Notizen

• Striated muscle tropomyosin (TM) interacts with actin and the troponin complex to regulate calcium-mediated muscle contraction. Previous work by our laboratory established that α- and β-TM isoforms elicit physiological differences in sarcomeric performance. Heart myofilaments containing β-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 β-TM is responsible for these physiological alterations, we exchanged the 27 terminal amino acids of α-TM (amino acids 258 –284) for the corresponding region in β-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.