Tyrosine and serine phosphorylation of the neural cell adhesion molecule L1 is implicated in its oligomannosidic glycan dependent association with NCAM and neurite outgrowth.
We have previously shown that a cis interaction between the cell adhesion molecules L1 and NCAM is mediated by N-linked oligomannosidic glycans carried by L1 and that this L1/NCAM association is involved in basal neurite outgrowth from early postnatal cerebellar neurons of mouse brain [R. Horstkorte et al., J. Cell Biol. 121, 1409-1421 (1993)]. Extending these earlier studies we investigated signal transduction mechanisms elicited by this molecular interaction. We show here that phosphorylation of L1 is reduced concomitant with reduced neurite outgrowth when the L1/NCAM interaction is inhibited by oligomannosidic glycopeptides. Similarly, when a peptide of the 4th immunoglobulin (Ig)-like domain of NCAM - representing part of NCAM's carbohydrate-binding site - was added to the culture medium of the cells, neurite outgrowth and phosphorylation of L1 was strongly reduced. No effect on neurite outgrowth and phosphorylation of L1 was observed when cells were maintained in the presence of a peptide comprising part of the 1st Ig-like domain of NCAM or in the presence of the peptide encoded by the variable alternative spliced exon (VASE), which is also located in the 4th Ig-like domain of NCAM. Furthermore, phosphorylation of tyrosine and serine residues of L1 is reduced when the L1/NCAM interaction at the cell surface of cerebellar neurons is perturbed. Our observations suggest that a signal transduction mechanism is implicated in basal neurite outgrowth in which both tyrosine and serine phosphorylation of L1 represent a possible proximal step. Some of these results were presented at the International Glycoconjugate Symposium in Seattle, USA [P. C. Heiland et al., Glycoconj. J. 12, 521(1995)].
Heiland
P C
PC
Department of Biochemistry, Institute of Animal Anatomy and Physiology, University of Bonn, Germany.
Griffith
L S
LS
Lange
R
R
Schachner
M
M
Hertlein
B
B
Traub
O
O
Schmitz
B
B
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000166:cytology; D050260:Carbohydrate Metabolism; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D039841:Leukocyte L1 Antigen Complex; D051379:Mice; D008969:Molecular Sequence Data; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009474:Neurons; D009842:Oligopeptides / Q000494:pharmacology; D009844:Oligosaccharides / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D039841:Leukocyte L1 Antigen Complex; D019006:Neural Cell Adhesion Molecules; D009842:Oligopeptides; D009844:Oligosaccharides; D010455:Peptides; D014443:Tyrosine; D012694:Serine