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

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 provided evidence demonstrating that adropin is a plasma membrane protein abundantly expressed in the brain. Using a yeast-two hybrid screening approach, we identified NB-3/Contactin6, a brain-specific non-canonical membrane-tethered Notch1 ligand, as an interaction partner of adropin. Furthermore, this interaction promotes NB3-induced activation of the Notch signaling and the expression of Notch target genes. We also generated and characterized the 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 present 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 may via NB-3/Notch signaling pathway and plays an important role in the cerebellum development in mice