| Structural highlights
Function
[NPTN_RAT] Probable homophilic and heterophilic cell adhesion molecule involved in long term potentiation at hippocampal excitatory synapses through activation of p38MAPK. May also regulate neurite outgrowth by activating the FGFR1 signaling pathway. May play a role in synaptic plasticity.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Neuroplastin-55 binds to and signals through the fibroblast growth factor receptor.,Owczarek S, Kiryushko D, Larsen MH, Kastrup JS, Gajhede M, Sandi C, Berezin V, Bock E, Soroka V FASEB J. 2010 Apr;24(4):1139-50. Epub 2009 Dec 1. PMID:19952283[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Smalla KH, Matthies H, Langnase K, Shabir S, Bockers TM, Wyneken U, Staak S, Krug M, Beesley PW, Gundelfinger ED. The synaptic glycoprotein neuroplastin is involved in long-term potentiation at hippocampal CA1 synapses. Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4327-32. PMID:10759566 doi:http://dx.doi.org/10.1073/pnas.080389297
- ↑ Empson RM, Buckby LE, Kraus M, Bates KJ, Crompton MR, Gundelfinger ED, Beesley PW. The cell adhesion molecule neuroplastin-65 inhibits hippocampal long-term potentiation via a mitogen-activated protein kinase p38-dependent reduction in surface expression of GluR1-containing glutamate receptors. J Neurochem. 2006 Nov;99(3):850-60. PMID:16925595 doi:http://dx.doi.org/10.1111/j.1471-4159.2006.04123.x
- ↑ Owczarek S, Kiryushko D, Larsen MH, Kastrup JS, Gajhede M, Sandi C, Berezin V, Bock E, Soroka V. Neuroplastin-55 binds to and signals through the fibroblast growth factor receptor. FASEB J. 2010 Apr;24(4):1139-50. Epub 2009 Dec 1. PMID:19952283 doi:10.1096/fj.09-140509
- ↑ Owczarek S, Kiryushko D, Larsen MH, Kastrup JS, Gajhede M, Sandi C, Berezin V, Bock E, Soroka V. Neuroplastin-55 binds to and signals through the fibroblast growth factor receptor. FASEB J. 2010 Apr;24(4):1139-50. Epub 2009 Dec 1. PMID:19952283 doi:10.1096/fj.09-140509
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