The role of cytoplasmic serine residues of the cell adhesion molecule L1 in neurite outgrowth, endocytosis, and cell migration.
1. The cell adhesion molecule L1 has been implicated in adhesion and migration of cells, in axon growth, guidance, and fasciculation, in myelination and synaptic plasticity. The cytoplasmic domain of neuronal L1 is highly conserved between species and has been shown to be phosphorylated at serine and tyrosine residues. 2. To investigate the significance of L1 serine phosphorylation, mutants of L1 were generated in which ser-1152, ser-1181, ser-1204, and ser-1248 were exchanged for leucine and rat B35 neuroblastoma cells were stably transfected with the L1-cDNA constructs. 3. Neurite outgrowth on poly-L-lysine (PLL) as substrate was determined either with or without differentiation into a neuronal phenotype with dbcAMP. In addition, antibody-induced endocytosis and cell migration were examined. 4. Our observations indicate that phosphorylation of single serine residues of the cytoplasmic domain of L1 contributes to neurite outgrowth through different mechanisms. Neurite growth is increased when ser-1152 or ser-1181 is replaced by a non-phosphorylatable leucine and decreased when ser-1204 or ser-1248 is mutated to leucine. Furthermore, mutation of ser-1181 to leucine results in strongly enhanced antibody-induced endocytosis of L1 and also in enhanced cell migration.
Schultheis
M
M
Department of Biochemistry, Institute of Animal Sciences, University of Bonn, Katzenburgweg 9a, 53115, Bonn, Germany.
Diestel
S
S
Schmitz
B
B
D000595:Amino Acid Sequence; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D003600:Cytosol / Q000737:chemistry; D004705:Endocytosis / Q000502:physiology*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D039842:Neural Cell Adhesion Molecule L1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016501:Neurites / Q000502:physiology*; D051381:Rats; D012694:Serine / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D039842:Neural Cell Adhesion Molecule L1; D012694:Serine