KETTIN, A LARGE MODULAR PROTEIN IN THE Z-DISC OF INSECT MUSCLES

Z-discs of insect flight muscle contain a large protein of 500-700 kDa . Monoclonal antibodies label an epitope in the molecule at the Z-disc in Drosophila and Lethocerus (waterbug). A partial cDNA of 1.6 kb fro m the Drosophila gene has been cloned and sequenced. The corresponding amino acid sequence has a modular structure composed of four conserve d repeats of 95 amino acids homologous to immunoglobulin C2 domains (c alled class II domains in muscle proteins), separated by less conserve d linker sequences of 35 amino acids. An expressed class II domain wit h flanking linker sequences binds to actin and alpha-actinin but not t o myosin. Single molecules of the protein would be large enough to spa n the Z-disc. We suggest that the protein acts as scaffolding in the Z -disc and we call the protein kettin. The Ca2+ activated protease, cal pain, disrupts the Z-disc of striated muscle, releasing alpha-actinin intact. Calpain digests kettin to a series of peptides of between 30 a nd 170 kDa which are released from the myofibril. Digestion of kettin may cause disintegration of the Z-disc and alpha-actinin release which lead to disassembly of the myofibril.