Ca2+-dependent Muscle Dysfunction Caused by Mutation of the Caenorhabditis elegans Troponin T-1 Gene

Title:
Ca2+-dependent Muscle Dysfunction Caused by Mutation of the Caenorhabditis elegans Troponin T-1 Gene
Authors:
McArdle, Kristen; Allen, Taylor; Bucher, Elizabeth A.
Abstract:
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.
Citation:
McArdle, Kristen, Taylor St. Claire Allen, and Elizabeth A. Bucher. 1998. "Ca2+-dependent Muscle Dysfunction Caused by Mutation of the Caenorhabditis elegans Troponin T-1 Gene." Journal of Cell Biology 143(5): 1201-1213.
Publisher:
Rockefeller University Press
DATE ISSUED:
1998-11-30
Department:
Biology
Type:
Article
PUBLISHED VERSION:
10.1083/jcb.143.5.1201
Additional Links:
http://www.jcb.org/lookup/doi/10.1083/jcb.143.5.1201
PERMANENT LINK:
http://hdl.handle.net/11282/597041

Full metadata record

DC FieldValue Language
dc.contributor.authorMcArdle, Kristenen
dc.contributor.authorAllen, Tayloren
dc.contributor.authorBucher, Elizabeth A.en
dc.date.accessioned2016-02-23T16:02:43Zen
dc.date.available2016-02-23T16:02:43Zen
dc.date.issued1998-11-30en
dc.identifier.citationMcArdle, Kristen, Taylor St. Claire Allen, and Elizabeth A. Bucher. 1998. "Ca2+-dependent Muscle Dysfunction Caused by Mutation of the Caenorhabditis elegans Troponin T-1 Gene." Journal of Cell Biology 143(5): 1201-1213.en
dc.identifier.issn0021-9525en
dc.identifier.urihttp://hdl.handle.net/11282/597041en
dc.description.abstractWe 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.en
dc.language.isoen_USen
dc.publisherRockefeller University Pressen
dc.identifier.doi10.1083/jcb.143.5.1201en
dc.relation.urlhttp://www.jcb.org/lookup/doi/10.1083/jcb.143.5.1201en
dc.subject.departmentBiologyen_US
dc.titleCa2+-dependent Muscle Dysfunction Caused by Mutation of the Caenorhabditis elegans Troponin T-1 Geneen_US
dc.typeArticleen
dc.identifier.journalThe Journal of Cell Biologyen
dc.identifier.volume143en_US
dc.identifier.issue5en_US
dc.identifier.startpage1201en_US
dc.rightsArchived with thanks to The Journal of Cell Biologyen
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