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© The Rockefeller University Press,
0021-9525/1998//1201 $5.00
The Journal of Cell Biology, Volume 143, Number 5,
, 1998 1201-1213
Article |
Ca2+-dependent Muscle Dysfunction Caused by Mutation of the Caenorhabditis elegans Troponin T-1 Gene
University of Washington, Department of Microbiology, Seattle, Washington 98195-7740; Oberlin College, Department of Biology, Oberlin, Ohio 44074-1082
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.
Key Words: troponin T • Caenorhabditis elegans • troponin C/troponin I interactions • human heart disease • Ca2+-regulation
Abbreviations used in this paper: ECM, extracellular matrix; Mup, muscle position defective; Pat, paralyzed and arrested elongation at twofold; Tm, tropomyosin; TnC, troponin C; TnI, troponin I; WT, wild-type.
The first two authors contributed equally to this work.
Address all correspondence to Elizabeth A. Bucher, University of Pennsylvania, Department of Cell and Developmental Biology, Pennsylvania Muscle Institute, School of Medicine, Philadelphia, PA 19104-6058. Tel.: (215) 898-2136. Fax: (215) 898-9871. E-mail: bucher{at}mail.med.upenn.edu
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