Adropin is a brain membrane-bound protein regulating physical activity via the NB-3/Notch signaling pathway in mice

J Biol Chem. 2014 Sep 12;289(37):25976-86. doi: 10.1074/jbc.M114.576058. Epub 2014 Jul 29.


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.

Keywords: Adropin; Energy Metabolism; Locomotor Activity Motor Coordination; Membrane Protein; Molecular Cell Biology; NB-3; Notch Pathway; Yeast Two-hybrid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Intercellular Signaling Peptides and Proteins
  • Ligands
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Motor Activity / genetics*
  • Motor Activity / physiology
  • Proteins / genetics
  • Proteins / metabolism*
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / metabolism*
  • Signal Transduction / genetics


  • Cell Adhesion Molecules, Neuronal
  • Enho protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Ligands
  • Membrane Proteins
  • Notch1 protein, mouse
  • Proteins
  • Receptor, Notch1
  • contactin 6 protein, mouse