TY - JOUR
T1 - Neuroplastin-55 binds to and signals through the fibroblast growth factor receptor
AU - Owczarek, Sylwia
AU - Kiryushko, Darya
AU - Larsen, Marianne Hald
AU - Kastrup, Jette Sandholm Jensen
AU - Gajhede, Michael
AU - Sandi, Carmen
AU - Berezin, Vladimir
AU - Bock, Elisabeth
AU - Soroka, Vladislav
PY - 2010/4
Y1 - 2010/4
N2 - 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.
AB - 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.
KW - Amino Acid Motifs
KW - Animals
KW - Antidepressive Agents
KW - Calcium
KW - Cell Line
KW - Crystallography, X-Ray
KW - Enzyme Activation
KW - Humans
KW - Membrane Glycoproteins
KW - Neurites
KW - Neuronal Plasticity
KW - Peptides
KW - Physical Conditioning, Animal
KW - Protein Binding
KW - Protein Structure, Tertiary
KW - Rats
KW - Rats, Wistar
KW - Receptor, Fibroblast Growth Factor, Type 1
KW - Signal Transduction
KW - Swimming
KW - Synapses
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1096/fj.09-140509
DO - 10.1096/fj.09-140509
M3 - Journal article
C2 - 19952283
SN - 0892-6638
VL - 24
SP - 1139
EP - 1150
JO - FASEB Journal
JF - FASEB Journal
IS - 4
ER -