Ca2+-dependent muscle dysfunction caused by mutation of the Caenorhabditiselegans troponin T-1 gene

We have investigated the functions of troponin T (CeTnT-1) in Caenorhabditi s elegans embryonic body wall muscle, TnT tethers troponin I (TnI) and trop onin C (TnC) to the thin filament via tropomyosin (Tm), and TnT/Tm regulate s the activation and inhibition of myosin-actin interaction in response to changes in intracellular [Ca2+]. Loss of CeTnT-1 function causes aberrant m uscle trembling and tearing of muscle cells from their exoskeletal attachme nt sites (Myers, C.D., P.-Y, Goh, T. StC. Alien, E.A. Bucher, and T. Bogaer t, 1996. J. Cell Biol, 132:1061-1077). We hypothesized that muscle tearing is a consequence of excessive force generation resulting from defective tet hering of Tn complex proteins, Biochemical studies suggest that such defect ive tethering would result in either (a) Ca2+-independent activation, due t o lack of Tn complex binding and consequent lack of inhibition, or (b) dela yed reestablishment of TnI/TnC binding to the thin filament after Ca2+ acti vation and consequent abnormal duration of force. Analyses of animals doubl y mutant for CeTnT-1 and for genes required for Ca2+ signaling support that CeTnT-1 phenotypes are dependent on Ca2+ signaling, thus supporting the se cond model and providing new in vivo evidence that full inhibition of thin filaments in low [Ca2+] does not require TnT.