Ca2+-dependent muscle dysfunction caused by mutation of the Caenorhabditis elegans troponin T-1 gene.
We have investigated the functions of troponin T (CeTnT-1) in Caenorhabditis elegans embryonic body wall muscle. TnT tethers troponin I (TnI) and troponin C (TnC) to the thin filament via tropomyosin (Tm), and TnT/Tm regulates the activation and inhibition of myosin-actin interaction in response to changes in intracellular [Ca2+]. Loss of CeTnT-1 function causes aberrant muscle trembling and tearing of muscle cells from their exoskeletal attachment sites (Myers, C.D., P.-Y. Goh, T. StC. Allen, E.A. Bucher, and T. Bogaert. 1996. J. Cell Biol. 132:1061-1077). We hypothesized that muscle tearing is a consequence of excessive force generation resulting from defective tethering of Tn complex proteins. Biochemical studies suggest that such defective tethering would result in either (a) Ca2+-independent activation, due to lack of Tn complex binding and consequent lack of inhibition, or (b) delayed reestablishment of TnI/TnC binding to the thin filament after Ca2+ activation and consequent abnormal duration of force. Analyses of animals doubly mutant for CeTnT-1 and for genes required for Ca2+ signaling support that CeTnT-1 phenotypes are dependent on Ca2+ signaling, thus supporting the second model and providing new in vivo evidence that full inhibition of thin filaments in low [Ca2+] does not require TnT.
McArdle
K
K
University of Pennsylvania, Department of Cell and Developmental Biology, Pennsylvania Muscle Institute, School of Medicine, Philadelphia, Pennsylvania 19104-6058, USA.
Allen
T S
TS
Bucher
E A
EA
D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics* / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000235:genetics; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000235:genetics / Q000502:physiology; D008954:Models, Biological; D009119:Muscle Contraction / Q000235:genetics / Q000502:physiology; D018482:Muscle, Skeletal / Q000196:embryology / Q000503:physiopathology*; D009154:Mutation; D010641:Phenotype; D013696:Temperature; D020107:Troponin T / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*
D015801:Helminth Proteins; D020107:Troponin T; D002118:Calcium