While much effort has focused on the role of the myosin head in dictating muscle contractile properties, our novel results indicate that the hinge of the rod also is critical for muscle function. We employ Drosophila melanogaster, which is amenable to genetic, transgenic and muscle mechanical approaches. Its single myosin gene encodes alternative myosin hinge regions, one expressed in slow twitch embryonic muscles and one expressed in fast twitch and oscillatory adult muscles.
Transgenic muscles assemble normal-looking myofibrils, but muscle function is severely compromised.
Our integrative approach should elucidate the role of the myosin hinge in muscle function and the mechanism by which it acts. Our work is relevant to human disease since mutations in myosin can cause hypertrophic cardiomyopathy in heart muscle and central core disease in skeletal muscle. Further, since the indirect flight muscle has oscillatory and stretch-activated properties similar to human cardiac muscle, understanding myosin s involvement in generating these properties may lead to insights into human heart function. Our approach will be integrated and multidisciplinary, with the application of molecular, biochemical, biophysical and genetic tools. We will employ the Drosophila melanogaster model system, since it provides a number of distinct advantages compared to vertebrate systems.