The neural cell adhesion molecule promotes FGFR-dependent phosphorylation and membrane targeting of the exocyst complex to induce exocytosis in growth cones.
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The neural cell adhesion molecule promotes FGFR-dependent phosphorylation and membrane targeting of the exocyst complex to induce exocytosis in growth cones. / Chernyshova, Yana; Leshchyns´ka, Iryna; Hsu, Shu-Chan; Schachner, Melitta; Sytnyk, Vladimir.
In: J NEUROSCI, Vol. 31, No. 10, 10, 2011, p. 3522-3535.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The neural cell adhesion molecule promotes FGFR-dependent phosphorylation and membrane targeting of the exocyst complex to induce exocytosis in growth cones.
AU - Chernyshova, Yana
AU - Leshchyns´ka, Iryna
AU - Hsu, Shu-Chan
AU - Schachner, Melitta
AU - Sytnyk, Vladimir
PY - 2011
Y1 - 2011
N2 - 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 Ca(2+)-dependent vesicle exocytosis, which is blocked by an inhibitor of L-type voltage-dependent Ca(2+) 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.
AB - 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 Ca(2+)-dependent vesicle exocytosis, which is blocked by an inhibitor of L-type voltage-dependent Ca(2+) 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.
KW - Animals
KW - Cells, Cultured
KW - Mice
KW - Mice, Knockout
KW - Enzyme-Linked Immunosorbent Assay
KW - Fluorescent Antibody Technique
KW - Phosphorylation
KW - Blotting, Western
KW - Calcium/metabolism
KW - Neural Cell Adhesion Molecules/genetics/metabolism
KW - Cell Membrane/metabolism
KW - Neurons/cytology/metabolism
KW - Calcium Channels, L-Type/metabolism
KW - Exocytosis/physiology
KW - Growth Cones/metabolism
KW - Hippocampus/cytology/metabolism
KW - Receptors, Fibroblast Growth Factor/metabolism
KW - Animals
KW - Cells, Cultured
KW - Mice
KW - Mice, Knockout
KW - Enzyme-Linked Immunosorbent Assay
KW - Fluorescent Antibody Technique
KW - Phosphorylation
KW - Blotting, Western
KW - Calcium/metabolism
KW - Neural Cell Adhesion Molecules/genetics/metabolism
KW - Cell Membrane/metabolism
KW - Neurons/cytology/metabolism
KW - Calcium Channels, L-Type/metabolism
KW - Exocytosis/physiology
KW - Growth Cones/metabolism
KW - Hippocampus/cytology/metabolism
KW - Receptors, Fibroblast Growth Factor/metabolism
M3 - SCORING: Journal article
VL - 31
SP - 3522
EP - 3535
JO - J NEUROSCI
JF - J NEUROSCI
SN - 0270-6474
IS - 10
M1 - 10
ER -