title: L1CAM increases MAP2 expression via the MAPK pathway to promote neurite outgrowth.
abstract: The neural cell adhesion molecule L1 (L1CAM) promotes neurite outgrowth via mechanisms that are not completely understood, but are known to involve the cytoskeleton. Here, we show that L1 binds directly to the microtubule associated protein 2c (MAP2c). This isoform of MAP2 is predominantly expressed in developing neurons. We found that the mRNA and protein levels of MAP2c, but not of MAP2a/b, are reduced in brains of young adult L1-deficient transgenic mice. We show via ELISA, that MAP2c, but not MAP2a/b, binds directly to the intracellular domain of L1. Remarkably, all these MAP2 isoforms co-immunoprecipitate with L1, suggesting that MAP2a/b associates with L1 via intermediate binding partners. The expression levels of MAP2a/b/c correlate with those of L1 in different brain regions of early postnatal mice, while expression levels of heat shock cognate protein 70 (Hsc70) or actin do not. L1 enhances the expression of MAP2a/b/c in cultured hippocampal neurons depending on activation of the mitogen-activated protein kinase (MAPK) pathway. Deficiency in both L1 and MAP2a/b/c expression results in reduced neurite outgrowth in vitro. We propose that the L1-triggered increase in MAP2a/b/c expression is required to promote neurite outgrowth.
authors.affiliation: Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Gunnar Heiko Dirk
authors.initials: GH
authors.lastname: Poplawski
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Tranziska
authors.forename: Iryna
authors.initials: I
authors.lastname: Leshchyns'ka
authors.forename: Ingo Dunya
authors.initials: ID
authors.lastname: Meier
authors.forename: Thomas
authors.initials: T
authors.lastname: Streichert
authors.forename: Vladimir
authors.initials: V
authors.lastname: Sytnyk
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
mesh_terms: D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D006579:Heterozygote; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000378:metabolism*; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D020033:Protein Isoforms / Q000378:metabolism
chemical_list: D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D039842:Neural Cell Adhesion Molecule L1; D020033:Protein Isoforms