Neuroplastin-65 and a mimetic peptide derived from its homophilic binding site modulate neuritogenesis and neuronal plasticity

Sylwia Owczarek; Vladislav Soroka; Darya Kiryushko; Marianne Hald Larsen; Qionglan Yuan; Carmen Sandi; Vladimir Berezin; Elisabeth Bock

doi:10.1111/j.1471-4159.2011.07269.x

Neuroplastin-65 and a mimetic peptide derived from its homophilic binding site modulate neuritogenesis and neuronal plasticity

J Neurochem. 2011 Jun;117(6):984-94. doi: 10.1111/j.1471-4159.2011.07269.x. Epub 2011 May 13.

Authors

Sylwia Owczarek¹, Vladislav Soroka, Darya Kiryushko, Marianne Hald Larsen, Qionglan Yuan, Carmen Sandi, Vladimir Berezin, Elisabeth Bock

Affiliation

¹ The Protein Laboratory, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark. sylwia@sund.ku.dk

PMID: 21480899
DOI: 10.1111/j.1471-4159.2011.07269.x

Abstract

Neuroplastin-65 (Np65) is a brain-specific cell adhesion molecule belonging to the immunoglobulin superfamily. Homophilic trans-interaction of Np65 mediates adhesion between cells and modulates synaptic plasticity. This interaction solely occurs through the first immunoglobulin (Ig) module of Np65, but the exact binding mechanism has not yet been elucidated. In this study, we identify the homophilic binding motif of Np65 and show that a synthetic peptide modeled after this motif, termed enplastin, binds to Np65. We demonstrate that both Np65- and enplastin-induced intracellular signaling depends on fibroblast growth factor receptor, p38 mitogen-activated protein kinase, Ca(2+) /calmodulin-dependent protein kinase, and cytoplasmic Ca(2+) concentration. In addition, we show that interference with Np65 homophilic binding by enplastin has an inhibitory effect on Np65-mediated neurite outgrowth in vitro and on the initial phase of spatial learning in rats.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Binding Sites
Calcium / metabolism
Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
Cells, Cultured
Cerebellum / cytology
Cerebellum / embryology
Cerebellum / metabolism
Enzyme Activation
Hippocampus / cytology
Hippocampus / embryology
Hippocampus / metabolism
Maze Learning / drug effects
Membrane Glycoproteins / genetics
Membrane Glycoproteins / physiology*
Mice
Mitogen-Activated Protein Kinases / metabolism
Molecular Mimicry
Neurites / drug effects
Neurites / physiology
Neuronal Plasticity* / drug effects
Neurons / cytology
Neurons / drug effects
Neurons / physiology*
Peptides / genetics
Peptides / pharmacology*
Protein Binding
Protein Isoforms / genetics
Protein Isoforms / physiology
Rats
Rats, Sprague-Dawley
Rats, Wistar
Receptors, Fibroblast Growth Factor / agonists
Recombinant Proteins / genetics
Recombinant Proteins / pharmacology

Substances

Membrane Glycoproteins
Nptn protein, rat
Peptides
Protein Isoforms
Receptors, Fibroblast Growth Factor
Recombinant Proteins
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Mitogen-Activated Protein Kinases
Calcium