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Neuroplastin‐55 binds to and signals through the fibroblast growth factor receptor
Author(s) -
Owczarek Sylwia,
Kiryushko Darya,
Larsen Marianne Hald,
Kastrup Jette Sandholm,
Gajhede Michael,
Sandi Carmen,
Berezin Vladimir,
Bock Elisabeth,
Soroka Vladislav
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-140509
Subject(s) - fibroblast growth factor receptor , fibroblast growth factor , microbiology and biotechnology , fibroblast growth factor receptor 3 , fibroblast growth factor receptor 4 , receptor , factor (programming language) , fibroblast growth factor receptor 2 , chemistry , medicine , biology , computer science , programming language
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 (Igl, Ig2, and Ig3), whereas Np55 lacks the Igl module. Of these two isoforms, only Np65 is involved in homophilic interactions resulting in cell adhesion, whereas the role of Np55 is poorlyunderstood. The present studyreports for the first time the crystal structure of the ectodomain of Np55 at 1.95‐Å 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. FASEB J. 24, 1139–1150 (2010). www.fasebj.org