title: Cardiac sodium channel regulator MOG1 regulates cardiac morphogenesis and rhythm.
abstract: MOG1 was initially identified as a protein that interacts with the small GTPase Ran involved in transport of macromolecules into and out of the nucleus. In addition, we have established that MOG1 interacts with the cardiac sodium channel Nav1.5 and regulates cell surface trafficking of Nav1.5. Here we used zebrafish as a model system to study the in vivo physiological role of MOG1. Knockdown of mog1 expression in zebrafish embryos significantly decreased the heart rate (HR). Consistently, the HR increases in embryos with over-expression of human MOG1. Compared with wild type MOG1 or control EGFP, mutant MOG1 with mutation E83D associated with Brugada syndrome significantly decreases the HR. Interestingly, knockdown of mog1 resulted in abnormal cardiac looping during embryogenesis. Mechanistically, knockdown of mog1 decreases expression of hcn4 involved in the regulation of the HR, and reduces expression of nkx2.5, gata4 and hand2 involved in cardiac morphogenesis. These data for the first time revealed a novel role that MOG1, a nucleocytoplasmic transport protein, plays in cardiac physiology and development.
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Center, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Center, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Longfei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Center, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Mengxia
authors.initials: M
authors.lastname: Zuo
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Center, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Center, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Abu Shufian Ishtiaq
authors.initials: AS
authors.lastname: Ahmed
authors.affiliation: Center for Cardiovascular Genetics, Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic; Department of Molecular Medicine, Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Qiuyun
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Center, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China.|Center for Cardiovascular Genetics, Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic; Department of Molecular Medicine, Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Qing K
authors.initials: QK
authors.lastname: Wang
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian; D029941:Fish Proteins / Q000235:genetics* / Q000378:metabolism; D050980:GATA Transcription Factors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005816:Genetic Complementation Test; D006321:Heart / Q000196:embryology; D006339:Heart Rate / Q000235:genetics*; D000072576:Homeobox Protein Nkx-2.5 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000235:genetics / Q000378:metabolism; D008845:Microinjections; D060172:Morpholinos / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism; D038081:Organogenesis / Q000235:genetics*; D016415:Sequence Alignment; D015027:Zebrafish / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D029941:Fish Proteins; D050980:GATA Transcription Factors; D000072576:Homeobox Protein Nkx-2.5; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D060172:Morpholinos; D062554:NAV1.5 Voltage-Gated Sodium Channel; D029961:Zebrafish Proteins; D020931:ran GTP-Binding Protein; C525957:Gata4 protein, zebrafish; C410915:hand2 protein, zebrafish; C498735:RANGNRF protein, human