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L1CAM binds ErbB receptors through Ig-like domains coupling cell adhesion and neuregulin signalling.

Donier, E; Gomez-Sanchez, JA; Grijota-Martinez, C; Lakomá, J; Baars, S; Garcia-Alonso, L; Cabedo, H; (2012) L1CAM binds ErbB receptors through Ig-like domains coupling cell adhesion and neuregulin signalling. PLoS One , 7 (7) , Article e40674. 10.1371/journal.pone.0040674. Green open access

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Abstract

During nervous system development different cell-to-cell communication mechanisms operate in parallel guiding migrating neurons and growing axons to generate complex arrays of neural circuits. How such a system works in coordination is not well understood. Cross-regulatory interactions between different signalling pathways and redundancy between them can increase precision and fidelity of guidance systems. Immunoglobulin superfamily proteins of the NCAM and L1 families couple specific substrate recognition and cell adhesion with the activation of receptor tyrosine kinases. Thus it has been shown that L1CAM-mediated cell adhesion promotes the activation of the EGFR (erbB1) from Drosophila to humans. Here we explore the specificity of the molecular interaction between L1CAM and the erbB receptor family. We show that L1CAM binds physically erbB receptors in both heterologous systems and the mammalian developing brain. Different Ig-like domains located in the extracellular part of L1CAM can support this interaction. Interestingly, binding of L1CAM to erbB enhances its response to neuregulins. During development this may synergize with the activation of erbB receptors through L1CAM homophilic interactions, conferring diffusible neuregulins specificity for cells or axons that interact with the substrate through L1CAM.

Type: Article
Title: L1CAM binds ErbB receptors through Ig-like domains coupling cell adhesion and neuregulin signalling.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0040674
Publisher version: htt://dx.doi.org/10.1371/journal.pone.0040674
Language: English
Additional information: © 2012 Donier et al. 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 credited.PMCID: PMC3398014
Keywords: Animals, Cell Adhesion, HEK293 Cells, Humans, Immunoglobulins, MCF-7 Cells, Neural Cell Adhesion Molecule L1, Neuregulins, Phosphorylation, Protein Binding, Protein Structure, Tertiary, Rats, Receptor, erbB-2, Receptor, erbB-3, Repetitive Sequences, Amino Acid, Signal Transduction, Structure-Activity Relationship
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: http://discovery.ucl.ac.uk/id/eprint/1388519
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