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 adhes ion molecules L1 and NCAM is mediated by N-linked oligomannosidic glyc ans carried by L1 and that this L1/NCAM association is involved in bas al neurite outgrowth from early postnatal cerebellar neurons of mouse brain [R. Horstkorte et al., J. Cell Biol. 121, 1409-1421 (1993)]. Ext ending these earlier studies we investigated signal transduction mecha nisms elicited by this molecular interaction. We show here that phosph orylation of L1 is reduced concomitant with reduced neurite outgrowth when the L1/NCAM interaction is inhibited by oligomannosidic glycopept ides. Similarly, when a peptide of the 4th immunoglobulin (Ig)-like do main of NCAM - representing part of NCAM's carbohydrate-binding site - was added to the culture medium of the cells, neurite outgrowth and p hosphorylation of L1 was strongly reduced. No effect on neurite outgro wth 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 alt ernative spliced exon (VASE), which is also located in the 4th Ig-like domain of NCAM. Furthermore, phosphorylation of tyrosine and serine r esidues of L1 is reduced when the L1/NCAM interaction at the cell surf ace of cerebellar neurons is perturbed. Our observations suggest that a signal transduction mechanism is implicated in basal neurite outgrow th in which both tyrosine and serine phosphorylation of L1 represent a possible proximal step. Some of these results were presented at the i nternational Glycoconjugate Symposium in Seattle, USA [P. C. Heiland e t al., Glycoconj. J. 12, 521 (1995)].