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A Peptide Mimetic Targeting Trans-Homophilic NCAM Binding Sites Promotes Spatial Learning and Neural Plasticity in the Hippocampus

The key roles played by the neural cell adhesion molecule (NCAM) in plasticity and cognition underscore this membrane protein as a relevant target to develop cognitive-enhancing drugs. However, NCAM is a structurally and functionally complex molecule with multiple domains engaged in a variety of act...

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Autores principales: Kraev, Igor, Henneberger, Christian, Rossetti, Clara, Conboy, Lisa, Kohler, Lene B., Fantin, Martina, Jennings, Alistair, Venero, Cesar, Popov, Victor, Rusakov, Dmitri, Stewart, Michael G., Bock, Elisabeth, Berezin, Vladimir, Sandi, Carmen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160849/
https://www.ncbi.nlm.nih.gov/pubmed/21887252
http://dx.doi.org/10.1371/journal.pone.0023433
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author Kraev, Igor
Henneberger, Christian
Rossetti, Clara
Conboy, Lisa
Kohler, Lene B.
Fantin, Martina
Jennings, Alistair
Venero, Cesar
Popov, Victor
Rusakov, Dmitri
Stewart, Michael G.
Bock, Elisabeth
Berezin, Vladimir
Sandi, Carmen
author_facet Kraev, Igor
Henneberger, Christian
Rossetti, Clara
Conboy, Lisa
Kohler, Lene B.
Fantin, Martina
Jennings, Alistair
Venero, Cesar
Popov, Victor
Rusakov, Dmitri
Stewart, Michael G.
Bock, Elisabeth
Berezin, Vladimir
Sandi, Carmen
author_sort Kraev, Igor
collection PubMed
description The key roles played by the neural cell adhesion molecule (NCAM) in plasticity and cognition underscore this membrane protein as a relevant target to develop cognitive-enhancing drugs. However, NCAM is a structurally and functionally complex molecule with multiple domains engaged in a variety of actions, which raise the question as to which NCAM fragment should be targeted. Synthetic NCAM mimetic peptides that mimic NCAM sequences relevant to specific interactions allow identification of the most promising targets within NCAM. Recently, a decapeptide ligand of NCAM—plannexin, which mimics a homophilic trans-binding site in Ig2 and binds to Ig3—was developed as a tool for studying NCAM's trans-interactions. In this study, we investigated plannexin's ability to affect neural plasticity and memory formation. We found that plannexin facilitates neurite outgrowth in primary hippocampal neuronal cultures and improves spatial learning in rats, both under basal conditions and under conditions involving a deficit in a key plasticity-promoting posttranslational modification of NCAM, its polysialylation. We also found that plannexin enhances excitatory synaptic transmission in hippocampal area CA1, where it also increases the number of mushroom spines and the synaptic expression of the AMPAR subunits GluA1 and GluA2. Altogether, these findings provide compelling evidence that plannexin is an important facilitator of synaptic functional, structural and molecular plasticity in the hippocampal CA1 region, highlighting the fragment in NCAM's Ig3 module where plannexin binds as a novel target for the development of cognition-enhancing drugs.
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spelling pubmed-31608492011-09-01 A Peptide Mimetic Targeting Trans-Homophilic NCAM Binding Sites Promotes Spatial Learning and Neural Plasticity in the Hippocampus Kraev, Igor Henneberger, Christian Rossetti, Clara Conboy, Lisa Kohler, Lene B. Fantin, Martina Jennings, Alistair Venero, Cesar Popov, Victor Rusakov, Dmitri Stewart, Michael G. Bock, Elisabeth Berezin, Vladimir Sandi, Carmen PLoS One Research Article The key roles played by the neural cell adhesion molecule (NCAM) in plasticity and cognition underscore this membrane protein as a relevant target to develop cognitive-enhancing drugs. However, NCAM is a structurally and functionally complex molecule with multiple domains engaged in a variety of actions, which raise the question as to which NCAM fragment should be targeted. Synthetic NCAM mimetic peptides that mimic NCAM sequences relevant to specific interactions allow identification of the most promising targets within NCAM. Recently, a decapeptide ligand of NCAM—plannexin, which mimics a homophilic trans-binding site in Ig2 and binds to Ig3—was developed as a tool for studying NCAM's trans-interactions. In this study, we investigated plannexin's ability to affect neural plasticity and memory formation. We found that plannexin facilitates neurite outgrowth in primary hippocampal neuronal cultures and improves spatial learning in rats, both under basal conditions and under conditions involving a deficit in a key plasticity-promoting posttranslational modification of NCAM, its polysialylation. We also found that plannexin enhances excitatory synaptic transmission in hippocampal area CA1, where it also increases the number of mushroom spines and the synaptic expression of the AMPAR subunits GluA1 and GluA2. Altogether, these findings provide compelling evidence that plannexin is an important facilitator of synaptic functional, structural and molecular plasticity in the hippocampal CA1 region, highlighting the fragment in NCAM's Ig3 module where plannexin binds as a novel target for the development of cognition-enhancing drugs. Public Library of Science 2011-08-24 /pmc/articles/PMC3160849/ /pubmed/21887252 http://dx.doi.org/10.1371/journal.pone.0023433 Text en Kraev et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kraev, Igor
Henneberger, Christian
Rossetti, Clara
Conboy, Lisa
Kohler, Lene B.
Fantin, Martina
Jennings, Alistair
Venero, Cesar
Popov, Victor
Rusakov, Dmitri
Stewart, Michael G.
Bock, Elisabeth
Berezin, Vladimir
Sandi, Carmen
A Peptide Mimetic Targeting Trans-Homophilic NCAM Binding Sites Promotes Spatial Learning and Neural Plasticity in the Hippocampus
title A Peptide Mimetic Targeting Trans-Homophilic NCAM Binding Sites Promotes Spatial Learning and Neural Plasticity in the Hippocampus
title_full A Peptide Mimetic Targeting Trans-Homophilic NCAM Binding Sites Promotes Spatial Learning and Neural Plasticity in the Hippocampus
title_fullStr A Peptide Mimetic Targeting Trans-Homophilic NCAM Binding Sites Promotes Spatial Learning and Neural Plasticity in the Hippocampus
title_full_unstemmed A Peptide Mimetic Targeting Trans-Homophilic NCAM Binding Sites Promotes Spatial Learning and Neural Plasticity in the Hippocampus
title_short A Peptide Mimetic Targeting Trans-Homophilic NCAM Binding Sites Promotes Spatial Learning and Neural Plasticity in the Hippocampus
title_sort peptide mimetic targeting trans-homophilic ncam binding sites promotes spatial learning and neural plasticity in the hippocampus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160849/
https://www.ncbi.nlm.nih.gov/pubmed/21887252
http://dx.doi.org/10.1371/journal.pone.0023433
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