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.
Highlights
The mechanism of action of adropin on metabolism remains elusive
Adropin knockout mice exhibited decreased locomotor activity and impaired motor coordination coupled with defective synapse formation, a phenotype similar to NB-3 knockout mice
The movement disorders may be due to the decrease in the reduction of NB-3 in the cerebellum and, cerebellar synapse formation in adropin knockout (adrKO) mice
Summary
The mechanism of action of adropin on metabolism remains elusive. Results: Adropin is a plasma membrane protein that can bind to the brain-specific, non-canonical Notch ligand NB-3. Using a yeast two-hybrid screening approach, we identified NB-3/Contactin 6, a brain-specific, non-canonical, membrane-tethered Notch ligand, as an interaction partner of adropin This interaction promotes NB3-induced activation of Notch signaling and the expression of Notch target genes. Our data suggest that adropin is a membrane-bound protein that interacts with the brain-specific Notch 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. Adropin, composed of 76 amino acids, is encoded by the energy homeostasis-associated (Enho) gene that is remarkably down-regulated in the livers of mice with high fat diet-induced obesity or genetic obesity because of melanocortin receptor. We characterized the expression and biochemical properties of adropin and investigated the central action of adropin in the mouse
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
