Work in this group is concerned with the assembly and function of the contractile machinery of striated muscle cells in health and disease. This machinery, called the myofibril, is composed of sarcomeres that contain interdigitating myosin and actin filaments. These filaments cyclically interact to produce force and shortening during muscle activation. Past work has demonstrated the importance of titin filaments in positioning the myosin filaments within the sarcomere, and in maintaining the structural integrity of the myofibril in relaxed muscle cells. More recently, we have demonstrated that relaxed muscle cells from various parts of the body have different mechanical properties due to the presence of different isoforms of the titin protein. Currently, we are utilizing molecular genetic approaches to study the role of large myofibrillar proteins, such as titin and nebulin, in myofibril assembly and function. To that end, we have obtained and sequenced several cDNA clones encoding regions of mouse nebulin. We have also obtained cDNA clones that encode a protein containing a nebulin-like domain, but that is much smaller than nebulin. We plan to express these proteins and study their function using a variety of cell and molecular biological techniques.
Horowits, R. Passive force generation and titin isoforms in mammalian skeletal muscle. Biophys J 61: 392-398, 1992.
Horowits, R., M. C. Dalakas and R. J. Podolsky. Single skinned muscle fibers in Duchenne muscular dystrophy generate normal force. Ann Neurol 27: 636-641, 1990.
Horowits, R., K. Maruyama and R. J. Podolsky. Elastic behavior of connectin filaments during thick filament movement in activated skeletal muscle. J Cell Biol 109: 2169-2176, 1989.
Document date: November 30, 1995