Schistosomes are parasitic worms infecting 200 million humans worldwide. Schistosomiasis is treated with the drug praziquantel, which affects the parasite muscle, possibly by binding to myosin light chains. To understand the molecular functioning of Schistosome muscles, we have studied their cellular and molecular makeup. EM sections of adult worms reveal exclusively smooth muscle throughout the body wall (thick filaments not in register, dense bodies instead of Z-lines). We carried out 3D-reconstruction of negatively stained, relaxed Schistosome thick filaments. Surprisingly, the reconstruction was indistinguishable from those obtained previously for arthropod striated muscles, showing a 4-fold helical arrangement of myosin interacting-head motifs. Published data show that only one myosin heavy chain (MHC) gene is expressed in Schistosoma mansoni. By proteomic-Mass Spectrometry (MS) analysis of myosin from the adult parasite stage we showed that this was similar to a striated, not smooth, MHC. Analysis of published protein sequences supports this finding. A percentage-of-identity distance tree, and alignment of multiple diverse MHC sequences, showed two main branches: one for vertebrate and invertebrate striated muscles, and a smooth and nonmuscle branch. The Schistosome MHC lies in the striated muscle group, completely separate from the smooth/nonmuscle group. The in vitro motility assay showed movement of Schistosome thin filaments over unregulated tarantula striated myosin filaments independent of calcium and similar to rabbit F-actin motility, suggesting the absence of thin filament regulation. In agreement with this result, proteomic-MS analysis of Schistosome filament homogenates demonstrated the expression of the thin filament components tropomyosin and actin, but no signal for troponin was detected. We conclude that Schistosome muscles are hybrids, containing striated muscle-like thick filaments (with striated muscle MHC) and smooth muscle-like thin filaments (no troponin), arranged in a smooth muscle-like architecture.
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