Requirements of Kettin, a giant muscle protein highly conserved in overallstructure in evolution, for normal muscle function, viability, and flight activity of Drosophila

Kettin is a giant muscle protein originally identified in insect flight mus cle Z-discs, Here, we determined the entire nucleotide sequence of Drosophi la melanogaster kettin, deduced the amino acid sequence of its protein prod uct (540 kD) along with that of the Caenorhabditis elegans counterpart, and found that the overall primary structure of Kettin has been highly conserv ed in evolution. The main body of Drosophila Kettin consists of 35 immunogl obulin C2 domains separated by spacers. The central two thirds of spacers a re constant in length and share in common two conserved motifs, putative ac tin binding sites. Neither fibronectin type III nor kinase domains were fou nd. Kettin is present at the Z-disc in several muscle types. Genetic analys is showed that kettin is essential for the formation and maintenance of nor mal sarcomere structure of muscles and muscle tendons. Accordingly, embryos lacking kettin activity cannot hatch nor can adult flies heterozygous for the kettin mutation fly.