Specific myosin heavy chain mutations suppress troponin I defects in Drosophila muscles

We show that specific mutations in the head of the thick filament molecule myosin heavy chain prevent a degenerative muscle syndrome resulting from th e hdp(2) mutation in the thin filament protein troponin I. One mutation del etes eight residues from the actin binding loop of myosin, while a second a ffects a residue at the base of this loop. Two other mutations affect amino acids near the site of nucleotide entry and exit in the motor domain. We d ocument the degree of phenotypic rescue each suppressor permits and show th at other point mutations in myosin, as well as null mutations, fail to supp ress the hdp(2) phenotype. We discuss mechanisms by which the hdp(2) phenot ypes are suppressed and conclude that the specific residues we identified i n myosin are important in regulating thick and thin filament interactions. This in vivo approach to dissecting the contractile cycle defines novel mol ecular processes that may be difficult to uncover by biochemical and struct ural analysis. Our study illustrates how expression of genetic defects are dependent upon genetic background, and therefore could have implications fo r understanding gene interactions in human disease.