Adropin Is a Brain Membrane-bound Protein Regulating Physical Activity via the NB-3/Notch Signaling Pathway in Mice |
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Authors: | Chi-Ming Wong Yudong Wang Jimmy Tsz Hang Lee Zhe Huang Donghai Wu Aimin Xu Karen Siu Ling Lam |
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Institution: | From the ‡State Key Laboratory of Pharmaceutical Biotechnology.;§Department of Medicine.;**Department of Pharmacology and Pharmacy.;¶Research Centre of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong and ;the ‖Guangzhou Institutes of Biomedicine and Health, Hong Kong, China |
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Abstract: | Adropin is a highly conserved polypeptide that has been suggested to act as an endocrine factor that plays important roles in metabolic regulation, insulin sensitivity, and endothelial functions. However, in this study, we provide evidence demonstrating that adropin is a plasma membrane protein expressed abundantly in the brain. Using a yeast two-hybrid screening approach, we identified NB-3/Contactin 6, a brain-specific, non-canonical, membrane-tethered Notch1 ligand, as an interaction partner of adropin. Furthermore, this interaction promotes NB3-induced activation of Notch signaling and the expression of Notch target genes. We also generated and characterized adropin knockout mice to explore the role of adropin in vivo. Adropin knockout mice exhibited decreased locomotor activity and impaired motor coordination coupled with defective synapse formation, a phenotype similar to NB-3 knockout mice. Taken together, our data suggest that adropin is a membrane-bound protein that interacts with the brain-specific Notch1 ligand NB3. It regulates physical activity and motor coordination via the NB-3/Notch signaling pathway and plays an important role in cerebellum development in mice. |
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Keywords: | Energy Metabolism Membrane Protein Molecular Cell Biology Notch Pathway Yeast Two-hybrid NB-3 Adropin Locomotor Activity Motor Coordination |
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