title: L1CAM binds ErbB receptors through Ig-like domains coupling cell adhesion and neuregulin signalling.
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.
authors: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-Spanish National Research Council, San Juan de Alicante, Spain.
authors: Emanuelle
authors: E
authors: Donier
authors: Jose Antonio
authors: JA
authors: Gomez-Sanchez
authors: Carmen
authors: C
authors: Grijota-Martinez
authors: Jarmila
authors: J
authors: Lakomá
authors: Sigrid
authors: S
authors: Baars
authors: Luis
authors: L
authors: Garcia-Alonso
authors: Hugo
authors: H
authors: Cabedo
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry*; D061986:MCF-7 Cells; D039842:Neural Cell Adhesion Molecule L1 / Q000737:chemistry* / Q000378:metabolism*; D020880:Neuregulins / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D007136:Immunoglobulins; D039842:Neural Cell Adhesion Molecule L1; D020880:Neuregulins; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3