Title :
Neuroplastin-55 binds to and signals through the fibroblast growth factor
receptor
Abstract :
- Neuroplastin ( Np ) is a glycoprotein belonging to the immunoglobulin superfamily of cell adhesion molecules (CAMs) and existing in two isoforms, Np55 and Np65 , named according to their molecular weights
- The extracellular part of Np65 contains three immunoglobulin (Ig)-like modules (Ig1, Ig2, and Ig3), whereas Np55 lacks the Ig1 module
- Of these two isoforms, only Np65 is involved in homophilic interactions resulting in cell adhesion, whereas the role of Np55 is poorly understood
- The present study reports for the first time the crystal structure of the ectodomain of Np55 at 1.95-A resolution and demonstrates that Np55 binds to and activates the fibroblast growth factor receptor 1 ( FGFR1 )
- Furthermore, we identify a sequence motif in the Ig2 module of Np55 interacting with FGFR1 and show that a synthetic peptide encompassing this motif, termed narpin , binds to and activates FGFR1
- We show that both Np55 and the narpin peptide induce neurite outgrowth through FGFR1 activation and that Np55 increases synaptic calcium concentration in an FGFR1-dependent manner
- Moreover, we demonstrate that narpin has an antidepressive-like effect in rats subjected to the forced swim test, suggesting that Np55-induced signaling may be involved in synaptic plasticity in vivo
- Owczarek, S., Kiryushko, D., Larsen, M. H., Kastrup, J. S., Gajhede, M., Sandi, C., Berezin, V., Bock, E., Soroka, V. Neuroplastin-55 binds to and signals through the fibroblast growth factor receptor