L1CAM increases MAP2 expression via the MAPK pathway to promote neurite outgrowth.
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L1CAM increases MAP2 expression via the MAPK pathway to promote neurite outgrowth. / Poplawski, Gunnar Heiko Dirk; Tranziska, Ann-Kathrin; Leshchyns´ka, Iryna; Meier, Ingo Dunya; Streichert, Thomas; Sytnyk, Vladimir; Schachner, Melitta.
in: MOL CELL NEUROSCI, Jahrgang 50, Nr. 2, 2, 2012, S. 169-178.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - L1CAM increases MAP2 expression via the MAPK pathway to promote neurite outgrowth.
AU - Poplawski, Gunnar Heiko Dirk
AU - Tranziska, Ann-Kathrin
AU - Leshchyns´ka, Iryna
AU - Meier, Ingo Dunya
AU - Streichert, Thomas
AU - Sytnyk, Vladimir
AU - Schachner, Melitta
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Animals
KW - Male
KW - Cells, Cultured
KW - Mice
KW - Mice, Knockout
KW - Heterozygote
KW - Oligonucleotide Array Sequence Analysis
KW - Gene Expression Profiling
KW - MAP Kinase Signaling System
KW - Mice, Inbred Strains
KW - Neural Cell Adhesion Molecule L1/genetics/metabolism
KW - Protein Isoforms/metabolism
KW - Brain/growth & development/metabolism
KW - Microtubule-Associated Proteins/biosynthesis/metabolism
KW - Neurites/enzymology/metabolism/physiology
KW - Animals
KW - Male
KW - Cells, Cultured
KW - Mice
KW - Mice, Knockout
KW - Heterozygote
KW - Oligonucleotide Array Sequence Analysis
KW - Gene Expression Profiling
KW - MAP Kinase Signaling System
KW - Mice, Inbred Strains
KW - Neural Cell Adhesion Molecule L1/genetics/metabolism
KW - Protein Isoforms/metabolism
KW - Brain/growth & development/metabolism
KW - Microtubule-Associated Proteins/biosynthesis/metabolism
KW - Neurites/enzymology/metabolism/physiology
M3 - SCORING: Journal article
VL - 50
SP - 169
EP - 178
JO - MOL CELL NEUROSCI
JF - MOL CELL NEUROSCI
SN - 1044-7431
IS - 2
M1 - 2
ER -