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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 â284) 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.