PALMITOYLATION OF NEUROFASCIN AT A SITE IN THE MEMBRANE-SPANNING DOMAIN HIGHLY CONSERVED AMONG THE L1 FAMILY OF CELL-ADHESION MOLECULES

This report presents the first evidence that a member of the L1 family of nervous system cell-adhesion molecules is covalently modified by t hioesterification with palmitate, and identifies a highly conserved cy steine in the predicted membrane-spanning domain as the site of modifi cation. Neurofascin is constitutively palmitoylated at cysteine-1213 a t close to a 1:1 molar stoichiometry. Kinetics of palmitate incorporat ion into neurofascin expressed in resting neuroblastoma cells indicate that the palmitate modification has the same turnover rate as the pol ypeptide chain and does not affect the protein stability of neurofasci n. Palmitoylation of neurofascin expressed in dorsal root ganglion neu rons is not required for delivery of neurofascin to the plasma membran e or targeting to axons. Palmitoylation also has no effect on ankyrin- binding activity of neurofascin, on the oligomeric state of neurofasci n in solution, or on cell-adhesion activity of neurofascin expressed i n neuroblastoma cells. A significant difference between native and C12 13L neurofascin is that these proteins were localized in distinct frac tions within a low-density membrane population enriched in signaling m olecules. These results indicate a palmitate-dependent targeting of ne urofascin to a specialized membrane microdomain.