Neuroplastin-55 binds to and signals through the fibroblast growth factor receptor

Sylwia Owczarek; Darya Kiryushko; Marianne Hald Larsen; Jette Sandholm Jensen Kastrup; Michael Gajhede; Carmen Sandi; Vladimir Berezin; Elisabeth Bock; Vladislav Soroka

doi:10.1096/fj.09-140509

Neuroplastin-55 binds to and signals through the fibroblast growth factor receptor

Sylwia Owczarek, Darya Kiryushko, Marianne Hald Larsen, Jette Sandholm Jensen Kastrup, Michael Gajhede, Carmen Sandi, Vladimir Berezin, Elisabeth Bock, Vladislav Soroka

34 Citations (Scopus)

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-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.

Original language	English
Journal	The FASEB Journal
Volume	24
Issue number	4
Pages (from-to)	1139-1150
Number of pages	12
ISSN	0892-6638
DOIs	https://doi.org/10.1096/fj.09-140509
Publication status	Published - Apr 2010

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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-{\AA} 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.",

author = "Sylwia Owczarek and Darya Kiryushko and {Hald Larsen}, Marianne and Kastrup, {Jette Sandholm Jensen} and Michael Gajhede and Carmen Sandi and Vladimir Berezin and Elisabeth Bock and Vladislav Soroka",

year = "2010",

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doi = "10.1096/fj.09-140509",

language = "English",

volume = "24",

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T1 - Neuroplastin-55 binds to and signals through the fibroblast growth factor receptor

AU - Owczarek, Sylwia

AU - Kiryushko, Darya

AU - Hald Larsen, Marianne

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-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.

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-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.

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 - The FASEB Journal

JF - The FASEB Journal

IS - 4

ER -

Neuroplastin-55 binds to and signals through the fibroblast growth factor receptor

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