The influence of the myosin converter domain on muscle function in Drosophila. Bernadette Glasheen, Seemanti Ramanath, Qian Wang, Debra Sheppard, Lauren Riley, Douglas Swank. Center for Biotechnology and Interdisciplinary Studies, Department of Biology, Rensselaer Polytechnic Institute, Troy, NY.

   Muscles must generate different amounts of force and operate at various speeds to power a wide variety of movements. A major protein component that is critical to setting these properties is the myosin isoform present in the muscle. However, how myosin isoform functional variation is determined by myosin structure is unknown. We studied the influence of the converter, a major myosin structural region, using Drosophila as it generates all myosin isoforms by alternative mRNA splicing from a single myosin heavy chain gene. The converter domain has five different alternative versions (11a-e), the most of the six alternative regions in the myosin gene. We created transgenic fly lines expressing myosin constructs that each contained a single alternative version of the converter and crossed them into the Mhc¹⁰ myosin null background. This forces expression of the four non-native converters (11b-e) in the indirect flight muscles (IFM). Currently, we have tested the 11b, 11d, and 11e lines and found that wing beat frequency for all three lines was 11-15% less than control lines, and flight ability was 34% lower in 11b and 11d lines and 42% lower in the 11e line. We measured the mechanical performance of isolated single muscle fibers and found that the 11b converter version decreased power production by 40% while 11d and 11e decreased power by 60%. Muscle speed (the frequency at which maximum power was generated) was also affected. 11e was the slowest, with a 44% decrease compared to control lines, followed by 36% for 11d, and 22% for 11b. Force production does not appear to be significantly altered by these converter regions. Thus, the converter is critical for setting optimal muscle power production and functions primarily by varying muscle speed.