Dennexin peptides modeled after the homophilic binding sites of the neural cell adhesion molecule (NCAM) promote neuronal survival, modify cell adhesion and impair spatial learning
| Autor: | Martina Fantin, Lene B. Køhler, Carmen Sandi, Clara Rossetti, Claus Christensen, Vladimir Berezin, Elisabeth Bock |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Models Molecular Identification Histology Neurite Molecular Sequence Data Growth-Factor Apoptosis Biology Fgl-Peptide Neuronal survival Cell Line Pathology and Forensic Medicine Mimetic peptides Rats Sprague-Dawley Mice Structural Biology Memory Subventricular Zone Cell Adhesion Neurites Animals Amino Acid Sequence Cerebellar Granule Neurons Rats Wistar Maze Learning Cell adhesion Neural Cell Adhesion Molecules Neurons Binding Sites Polysialic acid Receptor Agonist Neurite outgrowth Cell Biology General Medicine Adhesion Peptide Fragments Rats Cell biology Neural cell adhesion molecule nervous system Ectodomain Biochemistry Signal transduction Intracellular EndoN Signal Transduction |
| Zdroj: | European Journal of Cell Biology. 89:817-827 |
| ISSN: | 0171-9335 |
| DOI: | 10.1016/j.ejcb.2010.07.007 |
| Popis: | Neural cell adhesion molecule (NCAM)-mediated cell adhesion results in activation of intracellular signaling cascades that lead to cellular responses such as neurite outgrowth, neuronal survival, and modulation of synaptic activity associated with cognitive processes. The crystal structure of the immunoglobulin (Ig) 1-2-3 fragment of the NCAM ectodomain has revealed novel mechanisms for NCAM homophilic adhesion. The present study addressed the biological significance of the so called dense zipper formation of NCAM. Two peptides, termed dennexinA and dennexinB, were modeled after the contact interfaces between Ig1 and Ig3 and between Ig2 and Ig2, respectively, observed in the crystal structure. Although the two dennexin peptides differed in amino acid sequence, they both modulated cell adhesion, reflected by inhibition of NCAM-mediated neurite outgrowth. Both dennexins also promoted neuronal survival, and the effect of dennexinA was independent of polysialic acid expression. Consistent with the effect of dennexinA on NCAM-mediated adhesion in vitro, the peptide impaired long-term memory retention in rats in the Morris water maze test. Thus, dennexins are novel site-specific pharmacological tools for elucidation of the role of NCAM in a variety of biological processes under normal and pathological conditions. |
| Databáze: | OpenAIRE |
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