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Localization and functional consequences of a direct interaction between TRIOBP-1 and hERG proteins in the heart.
Jones, David K; Johnson, Ashley C; Roti Roti, Elon C; Liu, Fang; Uelmen, Rebecca; Ayers, Rebecca A; Baczko, Istvan; Tester, David J; Ackerman, Michael J; Trudeau, Matthew C; Robertson, Gail A.
Afiliación
  • Jones DK; Department of Neuroscience, Wisconsin Institutes for Medical Research, University of Wisconsin-Madison SMPH, 1111 Highland Ave. #5505, Madison, WI 53705, USA.
  • Johnson AC; Department of Physiology, University of Maryland School of Medicine, 660 W. Redwood St., Baltimore, MD 21201, USA.
  • Roti Roti EC; Department of Neuroscience, Wisconsin Institutes for Medical Research, University of Wisconsin-Madison SMPH, 1111 Highland Ave. #5505, Madison, WI 53705, USA.
  • Liu F; Department of Neuroscience, Wisconsin Institutes for Medical Research, University of Wisconsin-Madison SMPH, 1111 Highland Ave. #5505, Madison, WI 53705, USA.
  • Uelmen R; Department of Neuroscience, Wisconsin Institutes for Medical Research, University of Wisconsin-Madison SMPH, 1111 Highland Ave. #5505, Madison, WI 53705, USA.
  • Ayers RA; Department of Neuroscience, Wisconsin Institutes for Medical Research, University of Wisconsin-Madison SMPH, 1111 Highland Ave. #5505, Madison, WI 53705, USA.
  • Baczko I; Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged 6720, Hungary.
  • Tester DJ; Department of Cardiovascular Diseases, Division of Heart Rhythm Service, Mayo Clinic, Rochester, NY 55905, USA.
  • Ackerman MJ; Department of Cardiovascular Diseases, Division of Heart Rhythm Service, Mayo Clinic, Rochester, NY 55905, USA.
  • Trudeau MC; Department of Physiology, University of Maryland School of Medicine, 660 W. Redwood St., Baltimore, MD 21201, USA garobert@wisc.edu mtrudeau@som.umaryland.edu.
  • Robertson GA; Department of Neuroscience, Wisconsin Institutes for Medical Research, University of Wisconsin-Madison SMPH, 1111 Highland Ave. #5505, Madison, WI 53705, USA garobert@wisc.edu mtrudeau@som.umaryland.edu.
J Cell Sci ; 131(6)2018 03 22.
Article en En | MEDLINE | ID: mdl-29507111
ABSTRACT
Reduced levels of the cardiac human (h)ERG ion channel protein and the corresponding repolarizing current IKr can cause arrhythmia and sudden cardiac death, but the underlying cellular mechanisms controlling hERG surface expression are not well understood. Here, we identified TRIOBP-1, an F-actin-binding protein previously associated with actin polymerization, as a putative hERG-interacting protein in a yeast-two hybrid screen of a cardiac library. We corroborated this interaction by performing Förster resonance energy transfer (FRET) in HEK293 cells and co-immunoprecipitation in HEK293 cells and native cardiac tissue. TRIOBP-1 overexpression reduced hERG surface expression and current density, whereas reducing TRIOBP-1 expression via shRNA knockdown resulted in increased hERG protein levels. Immunolabeling in rat cardiomyocytes showed that native TRIOBP-1 colocalized predominantly with myosin-binding protein C and secondarily with rat ERG. In human stem cell-derived cardiomyocytes, TRIOBP-1 overexpression caused intracellular co-sequestration of hERG signal, reduced native IKr and disrupted action potential repolarization. Ca2+ currents were also somewhat reduced and cell capacitance was increased. These findings establish that TRIOBP-1 interacts directly with hERG and can affect protein levels, IKr magnitude and cardiac membrane excitability.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Miocitos Cardíacos / Proteínas de Microfilamentos Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: J Cell Sci Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Miocitos Cardíacos / Proteínas de Microfilamentos Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: J Cell Sci Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos