VASE-ENCODED PEPTIDE MODIFIES NCAM-MEDIATED AND L1-MEDIATED NEURITE OUTGROWTH

Interactions between the neural cell adhesion molecule (NCAM) with NCA M-expressing neurons (transinteraction) stimulate outgrowth of neurite s. The extent of NCAM-triggered neurite outgrowth depends on the prese nce of 10 amino acids derived from the variable alternatively spliced exon (VASE or pi-exon) in the fourth immunoglobulin-like domain of NCA M (Ig4): NCAM with VASE reduces and without VASE enhances neurite outg rowth in cis- or trans-interaction. We have investigated the role of V ASE in neurite outgrowth by characterizing the receptors at the cell s urface of cultured cerebellar neurons. Results from experiments with L 1 and NCAM antibodies and with cerebellar neurons derived from wild-ty pe or NCAM-deficient mice show that substrate-coated Ig4 with VASE (Ig 4+) or without VASE (Ig4-) stimulates neurite outgrowth by a trans-int eraction with L1 and that Ig4- promotes neurite outgrowth more strongl y than Ig4+ by a transinteraction with NCAM. (C) 1997 Wiley-Liss, Inc.