title: Binding of the receptor tyrosine kinase TrkB to the neural cell adhesion molecule (NCAM) regulates phosphorylation of NCAM and NCAM-dependent neurite outgrowth.
abstract: Recognition molecules and neurotrophins play important roles during development and maintenance of nervous system functions. In this study, we provide evidence that the neural cell adhesion molecule (NCAM) and the neurotrophin receptor TrkB directly interact via sequences in their intracellular domains. Stimulation of TrkB by brain-derived neurotrophic factor leads to tyrosine phosphorylation of NCAM at position 734. Mutation of this tyrosine to phenylalanine completely abolishes tyrosine phosphorylation of NCAM by TrkB. Moreover, the knockdown of TrkB in hippocampal neurons leads to a reduction of NCAM-induced neurite outgrowth. Transfection of NCAM-deficient hippocampal neurons with mutated NCAM carrying an exchange of tyrosine by phenylalanine at position 734 leads to promotion of NCAM-induced neurite outgrowth in comparison with that observed after transfection with wild-type NCAM, whereas a reduction of neurite outgrowth was observed after transfection with mutated NCAM, which carries an exchange of tyrosine by glutamate that mimics the phosphorylated tyrosine. Our observations indicate a functional relationship between TrkB and NCAM.
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universität Hamburg, Martinistrasse 85, 20246 Hamburg, Germany.
authors.forename: Claas
authors.initials: C
authors.lastname: Cassens
authors.forename: Ralf
authors.initials: R
authors.lastname: Kleene
authors.forename: Mei-Fang
authors.initials: MF
authors.lastname: Xiao
authors.forename: Claudia
authors.initials: C
authors.lastname: Friedrich
authors.forename: Galina
authors.initials: G
authors.lastname: Dityateva
authors.forename: Claus
authors.initials: C
authors.lastname: Schafer-Nielsen
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D017434:Protein Structure, Tertiary; D051381:Rats; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D019006:Neural Cell Adhesion Molecules; D020813:Receptor, trkB