The Neural Cell Adhesion Molecule Promotes FGFR-Dependent Phosphorylation and Membrane Targeting of the Exocyst Complex to Induce Exocytosis in Growth Cones
Copyright policy )The Neural Cell Adhesion Molecule Promotes FGFR-Dependent Phosphorylation and Membrane Targeting of the Exocyst Complex to Induce Exocytosis in Growth Cones
The exocyst complex is an essential regulator of polarized exocytosis involved in morphogenesis of neurons. We show that this complex binds to the intracellular domain of the neural cell adhesion molecule (NCAM). NCAM promotes FGF receptor-mediated phosphorylation of two tyrosine residues in the sec8 subunit of the exocyst complex and is required for efficient recruitment of the exocyst complex to growth cones. NCAM at the surface of growth cones induces Ca2+-dependent vesicle exocytosis, which is blocked by an inhibitor of L-type voltage-dependent Ca2+channels and tetanus toxin. Preferential exocytosis in growth cones underlying neurite outgrowth is inhibited in NCAM-deficient neurons as well as in neurons transfected with phosphorylation-deficient sec8 and dominant-negative peptides derived from the intracellular domain of NCAM. Thus, we reveal a novel role for a cell adhesion molecule in that it regulates addition of the new membrane to the cell surface of growth cones in developing neurons.
- Universität Hamburg Germany
- University Medical Center Hamburg-Eppendorf Germany
- UNSW Sydney Australia
Mice, Knockout, Neurons, Calcium Channels, L-Type, Blotting, Western, Cell Membrane, Growth Cones, Fluorescent Antibody Technique, Enzyme-Linked Immunosorbent Assay, Hippocampus, Receptors, Fibroblast Growth Factor, Exocytosis, Mice, Animals, Calcium, Phosphorylation, Neural Cell Adhesion Molecules, Cells, Cultured
Mice, Knockout, Neurons, Calcium Channels, L-Type, Blotting, Western, Cell Membrane, Growth Cones, Fluorescent Antibody Technique, Enzyme-Linked Immunosorbent Assay, Hippocampus, Receptors, Fibroblast Growth Factor, Exocytosis, Mice, Animals, Calcium, Phosphorylation, Neural Cell Adhesion Molecules, Cells, Cultured
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