FIGQY phosphorylation defines discrete populations of L1 cell adhesion molecules at sites of cell-cell contact and in migrating neurons

Phosphorylation of neurofascin, a member of the L1 family of cell adhesion molecules (L1 CAMs), at the conserved FIGQY-tyrosine abolishes the ankyrin- neurofascin interaction. This study provides the first evidence, in Drosoph ila melanogaster and vertebrates, for the physiological occurrence of FIGQY phosphorylation in L1 family members. FIGQY tyrosine phosphorylation is lo calized at specialized cell junctions, including paranodes of sciatic nerve , neuromuscular junctions of adult rats and Drosophila embryos, epidermal m uscle attachment sites: of Drosophila, and adherens junctions of developing epithelial cells of rat and Drosophila. In addition, FIGQY-phosphorylated L1 CAMs are abundantly expressed in regions of neuronal migration and axon extension, including the embryonic cortex, the neonatal cerebellum and the rostral migratory stream, a region of continued neurogenesis and migration throughout adulthood in the rat. Based on our results, physiological FIGQY- tyrosine phosphorylation of the L1 family likely regulates adhesion molecul e-ankyrin interactions establishing ankyrin-free and ankyrin-containing mic rodomains and participates in an ankyrin-independent intracellular signalin g pathway at specialized sites of intercellular contact in epithelial and n ervous tissue.