During the past 7 years, it has become apparent that the myofilament lattice of invertebrates possess very large (>700,000 Da) polypeptides consisting primarily of immunoglobulin (Ig) and fibronectin type III (FnIII) domains. The founding member of this group was C. elegans twitchin, encoded by the mutationally defined gene
unc-22. Twitchin, located in the thick filament containing A-bands, functions both in regulating muscle contraction, and in the final stages of sarcomere assembly. Genetic analysis of
unc-22 provided important clues as to the function of twitchin before the gene was cloned and sequenced. The sequence provided the first example of an intracellular protein which belonged to the Ig superfamily. Although the substrate for nematode twitchin is not known, it has been shown to be autoinhibited by 60 amino acid residues lying just C-terminal to the kinase catalytic core. The structural basis for this autoinhibition has been determined by solving the crystal structure of twitchin kinase. Similar proteins have been discovered in honeybees, Lethocerus, scallop, Drosophila, and Aplysia. The similar protein in Drosophil, called projectin, is present in two isoforms, encoded by a single gene. A smaller polypeptide is located in the I-bands of asynchronous muscles, and a larger polypeptide is located in the A-bands of synchronous muscles. Both isoforms appear to have protein kinase activity. Homozygous mutations in the projectin gene result in embryonic or larval lethality, indicating an essential role in muscle formation....