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

TY - JOUR

T1 - Neuroplastin-65 and a mimetic peptide derived from its homophilic binding site modulate neuritogenesis and neuronal plasticity

AU - Owczarek, Sylwia

AU - Soroka, Vladislav

AU - Kiryushko, Darya

AU - Larsen, Marianne Hald

AU - Yuan, Qionglan

AU - Sandi, Carmen

AU - Berezin, Vladimir

AU - Bock, Elisabeth

N1 - © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

PY - 2011/6

Y1 - 2011/6

N2 - 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.

AB - 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.

KW - Animals

KW - Binding Sites

KW - Calcium

KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2

KW - Cells, Cultured

KW - Cerebellum

KW - Enzyme Activation

KW - Hippocampus

KW - Maze Learning

KW - Membrane Glycoproteins

KW - Mice

KW - Mitogen-Activated Protein Kinases

KW - Molecular Mimicry

KW - Neurites

KW - Neuronal Plasticity

KW - Neurons

KW - Peptides

KW - Protein Binding

KW - Protein Isoforms

KW - Rats

KW - Rats, Sprague-Dawley

KW - Rats, Wistar

KW - Receptors, Fibroblast Growth Factor

KW - Recombinant Proteins

U2 - 10.1111/j.1471-4159.2011.07269.x

DO - 10.1111/j.1471-4159.2011.07269.x

M3 - Journal article

C2 - 21480899

SN - 0022-3042

VL - 117

SP - 984

EP - 994

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

IS - 6

ER -