title: Neuroplastin-65 and a mimetic peptide derived from its homophilic binding site modulate neuritogenesis and neuronal plasticity.
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.
authors.affiliation: The Protein Laboratory, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark. sylwia@sund.ku.dk
authors.forename: Sylwia
authors.initials: S
authors.lastname: Owczarek
authors.forename: Vladislav
authors.initials: V
authors.lastname: Soroka
authors.forename: Darya
authors.initials: D
authors.lastname: Kiryushko
authors.forename: Marianne Hald
authors.initials: MH
authors.lastname: Larsen
authors.forename: Qionglan
authors.initials: Q
authors.lastname: Yuan
authors.forename: Carmen
authors.initials: C
authors.lastname: Sandi
authors.forename: Vladimir
authors.initials: V
authors.lastname: Berezin
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bock
mesh_terms: D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D004789:Enzyme Activation; D006624:Hippocampus / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018716:Molecular Mimicry; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000235:genetics / Q000494:pharmacology*; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017468:Receptors, Fibroblast Growth Factor / Q000819:agonists; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology
chemical_list: D008562:Membrane Glycoproteins; C548934:Nptn protein, rat; D010455:Peptides; D020033:Protein Isoforms; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium