PUBLICATION
Cardiac sodium channel regulator MOG1 regulates cardiac morphogenesis and rhythm
- Authors
- Zhou, J., Wang, L., Zuo, M., Wang, X., Ahmed, A.S., Chen, Q., Wang, Q.K.
- ID
- ZDB-PUB-160224-5
- Date
- 2016
- Source
- Scientific Reports 6: 21538 (Journal)
- Registered Authors
- Keywords
- Cardiovascular biology, Morphogenesis
- MeSH Terms
-
- Active Transport, Cell Nucleus/genetics
- Amino Acid Sequence
- Animals
- Base Sequence
- Basic Helix-Loop-Helix Transcription Factors/genetics
- Basic Helix-Loop-Helix Transcription Factors/metabolism
- Embryo, Nonmammalian
- Fish Proteins/genetics*
- Fish Proteins/metabolism
- GATA Transcription Factors/genetics
- GATA Transcription Factors/metabolism
- Gene Expression Regulation, Developmental*
- Genetic Complementation Test
- Heart/embryology
- Heart Rate/genetics*
- Homeobox Protein Nkx-2.5/genetics
- Homeobox Protein Nkx-2.5/metabolism
- Humans
- Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/genetics
- Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/metabolism
- Microinjections
- Morpholinos/genetics
- Morpholinos/metabolism
- Mutation
- NAV1.5 Voltage-Gated Sodium Channel/genetics
- NAV1.5 Voltage-Gated Sodium Channel/metabolism
- Organogenesis/genetics*
- Sequence Alignment
- Zebrafish/embryology
- Zebrafish/genetics*
- Zebrafish/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- ran GTP-Binding Protein/antagonists & inhibitors
- ran GTP-Binding Protein/genetics*
- ran GTP-Binding Protein/metabolism
- PubMed
- 26903377 Full text @ Sci. Rep.
Citation
Zhou, J., Wang, L., Zuo, M., Wang, X., Ahmed, A.S., Chen, Q., Wang, Q.K. (2016) Cardiac sodium channel regulator MOG1 regulates cardiac morphogenesis and rhythm. Scientific Reports. 6:21538.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping