A tropomyosin-2 mutation suppresses a troponin I myopathy in Drosophila

A suppressor mutation, D53, of the held-up(2) allele of the Drosophila mela nogaster Troponin I (wupA) gene is described. D53, a missense mutation, S18 5F, of the tropomyosin-2, Tm2, gene fully suppresses all the phenotypic eff ects of held-up(2), including the destructive hypercontraction of the indir ect flight muscles (IFMs), a lack of jumping, the progressive myopathy of t he walking muscles, and reductions in larval crawling and feeding behavior. The suppressor restores normal function of the IFMs, but flight ability de creases with age and correlates with an unusual, progressive structural col lapse of the myofibrillar lattice starting at the center. The S185F substit ution in Tm2 is close to a troponin T binding site on tropomyosin. Models t o explain suppression by D53, derived from current knowledge of the vertebr ate troponin-tropomyosin complex structure and functions, are discussed. Th e effects of S185F are compared with those of two mutations in residues 175 and 180 of human alpha -tropomyosin 1 which cause familial hypertrophic ca rdiomyopathy (HCM).