Traveling for Care?
Whether you're crossing the country or the globe, we make it easy to access world-class care at Johns Hopkins.
Myosin Transducer Mutation Differentially Affect Motor Function, Myogibril Structure, and the Performance of Skeletal and Cardiac Muscles
Anthony Cammarato, Corey M. Dambacher, Aileen F. Knowles, William A. Kronert, Rolf Bodmer, Karen Ocorr, and Sanford I. Bernstein
Drosophila, which have a single muscle myosin gene whose splice variants are expressed in every striated muscle, are an ideal model system for analyzing the pathological consequences of mutations that alter the motor's chemomechanical properties. The authors have studied two mutations located in the transducer domain of the muscle myosin motor, D45 and Mhc5, which, respectively, decrease and increase ATPase activity and motility in vitro. The hypoactive D45 mutant protects against age-associated dysfunction of metabolically demanding skeletral muscles but causes a dilated cardiomyopathy phenotype similar to that seen in human patients with hypoactive cardiac myosin mutations. In contrast, the hyperactive Mhc5 mutant disrupts the ulatrstructure and function of skeletal muscles, reflecting disinhibition and hypercontraction. The cardiac phenotype in Mhc5-expressing flies resembles a rare myocardial disorder, human restricive cardiomyopathy, that although not previously linked to myosin mutations is associated with dysregulation of motor activity. The authors' prediction that Drosophila may serve as a useful model in this regard has been borne out by very recent documentation that a myosin mutation causes pediatric restrictive cardiomyopathy. (S.M. Ware, et al., Clin. Genetic., in press).