A peptide derived from a trans-homophilic binding site in neural cell adhesion molecule induces neurite outgrowth and neuronal survival

TY - JOUR

T1 - A peptide derived from a trans-homophilic binding site in neural cell adhesion molecule induces neurite outgrowth and neuronal survival

AU - Køhler, Lene B

AU - Soroka, Vladislav

AU - Korshunova, Irina

AU - Berezin, Vladimir

AU - Bock, Elisabeth

PY - 2010/8/1

Y1 - 2010/8/1

N2 - The neural cell adhesion molecule (NCAM) plays a key role in neural development, regeneration, and synaptic plasticity. The crystal structure of a fragment of NCAM comprising the three N-terminal immunoglobulin (Ig)-like modules indicates that the first and second Ig modules bind to each other, thereby presumably mediating dimerization of NCAM molecules expressed on the same cell surface (cis-interactions), whereas the third Ig module, through interactions with the first or second Ig module, mediates interactions between NCAM molecules expressed on the surface of opposing cells (trans-interactions). We have designed a new potent peptide ligand of NCAM, termed plannexin, based on a discontinuous sequence in the second NCAM Ig module that represents a homophilic binding site for an opposing third Ig module. The peptide was found by surface plasmon resonance analysis to bind the third NCAM Ig module. It promoted survival of cultured cerebellar granule neurons (CGNs) and also induced neurite extension in cultures of dopaminergic neurons and CGNs; the latter effect was shown to be dependent on NCAM expression, indicating that plannexin mimics the neuritogenic effect of homophilic NCAM binding.

AB - The neural cell adhesion molecule (NCAM) plays a key role in neural development, regeneration, and synaptic plasticity. The crystal structure of a fragment of NCAM comprising the three N-terminal immunoglobulin (Ig)-like modules indicates that the first and second Ig modules bind to each other, thereby presumably mediating dimerization of NCAM molecules expressed on the same cell surface (cis-interactions), whereas the third Ig module, through interactions with the first or second Ig module, mediates interactions between NCAM molecules expressed on the surface of opposing cells (trans-interactions). We have designed a new potent peptide ligand of NCAM, termed plannexin, based on a discontinuous sequence in the second NCAM Ig module that represents a homophilic binding site for an opposing third Ig module. The peptide was found by surface plasmon resonance analysis to bind the third NCAM Ig module. It promoted survival of cultured cerebellar granule neurons (CGNs) and also induced neurite extension in cultures of dopaminergic neurons and CGNs; the latter effect was shown to be dependent on NCAM expression, indicating that plannexin mimics the neuritogenic effect of homophilic NCAM binding.

KW - Animals

KW - Cell Enlargement

KW - Cell Line, Tumor

KW - Cell Survival

KW - Cells, Cultured

KW - Cerebellum

KW - Dopamine

KW - Ligands

KW - Mesencephalon

KW - Mice

KW - Neural Cell Adhesion Molecules

KW - Neurites

KW - Neurons

KW - Oligopeptides

KW - Peptides

KW - Protein Binding

KW - Rats

KW - Rats, Wistar

U2 - 10.1002/jnr.22380

DO - 10.1002/jnr.22380

M3 - Journal article

C2 - 20209630

SN - 0360-4012

VL - 88

SP - 2165

EP - 2176

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

IS - 10

ER -