title: Troponin T3 regulates nuclear localization of the calcium channel Cavβ1a subunit in skeletal muscle.
abstract: The voltage-gated calcium channel (Cav) β1a subunit (Cavβ1a) plays an important role in excitation-contraction coupling (ECC), a process in the myoplasm that leads to muscle-force generation. Recently, we discovered that the Cavβ1a subunit travels to the nucleus of skeletal muscle cells where it helps to regulate gene transcription. To determine how it travels to the nucleus, we performed a yeast two-hybrid screening of the mouse fast skeletal muscle cDNA library and identified an interaction with troponin T3 (TnT3), which we subsequently confirmed by co-immunoprecipitation and co-localization assays in mouse skeletal muscle in vivo and in cultured C2C12 muscle cells. Interacting domains were mapped to the leucine zipper domain in TnT3 COOH-terminus (160-244 aa) and Cavβ1a NH2-terminus (1-99 aa), respectively. The double fluorescence assay in C2C12 cells co-expressing TnT3/DsRed and Cavβ1a/YFP shows that TnT3 facilitates Cavβ1a nuclear recruitment, suggesting that the two proteins play a heretofore unknown role during early muscle differentiation in addition to their classical role in ECC regulation.
authors.affiliation: Department of Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Tan
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Jackson
authors.initials: J
authors.lastname: Taylor
authors.affiliation: Department of Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Histology, National University of La Plata, 1900 La Plata, Argentina.
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Pereyra
authors.affiliation: Department of Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Messi
authors.affiliation: Department of Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Zhong-Min
authors.initials: ZM
authors.lastname: Wang
authors.affiliation: Department of Histology, National University of La Plata, 1900 La Plata, Argentina.
authors.forename: Claudia
authors.initials: C
authors.lastname: Hereñú
authors.affiliation: Department of Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA; Neuroscience Program, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. Electronic address: odelbono@wakehealth.edu.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Delbono
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D056966:Excitation Contraction Coupling / Q000502:physiology*; D015723:Gene Library; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D014336:Troponin / Q000378:metabolism*
chemical_list: C492923:Cacnb1 protein, mouse; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D014336:Troponin; C587363:troponin T3, skeletal, fast, mouse; D002118:Calcium
keywords: Ca(v)β(1a); Nuclear localization; Skeletal muscle; Troponin T3