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, Jahrgang 31, Nr. 10, 10, 2011, S. 3522-3535.

Publikationen: SCORING: Beitrag in Fachzeitschrift/ZeitungSCORING: ZeitschriftenaufsatzForschungBegutachtung

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Bibtex

@article{28500bc756764591beb03ca0e049ae90,
title = "The neural cell adhesion molecule promotes FGFR-dependent phosphorylation and membrane targeting of the exocyst complex to induce exocytosis in growth cones.",
abstract = "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.",
keywords = "Animals, Cells, Cultured, Mice, Mice, Knockout, Enzyme-Linked Immunosorbent Assay, Fluorescent Antibody Technique, Phosphorylation, Blotting, Western, Calcium/metabolism, Neural Cell Adhesion Molecules/genetics/*metabolism, Cell Membrane/metabolism, Neurons/cytology/*metabolism, Calcium Channels, L-Type/metabolism, Exocytosis/*physiology, Growth Cones/*metabolism, Hippocampus/cytology/metabolism, Receptors, Fibroblast Growth Factor/*metabolism, Animals, Cells, Cultured, Mice, Mice, Knockout, Enzyme-Linked Immunosorbent Assay, Fluorescent Antibody Technique, Phosphorylation, Blotting, Western, Calcium/metabolism, Neural Cell Adhesion Molecules/genetics/*metabolism, Cell Membrane/metabolism, Neurons/cytology/*metabolism, Calcium Channels, L-Type/metabolism, Exocytosis/*physiology, Growth Cones/*metabolism, Hippocampus/cytology/metabolism, Receptors, Fibroblast Growth Factor/*metabolism",
author = "Yana Chernyshova and Iryna Leshchyns´ka and Shu-Chan Hsu and Melitta Schachner and Vladimir Sytnyk",
year = "2011",
language = "English",
volume = "31",
pages = "3522--3535",
journal = "J NEUROSCI",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "10",

}

RIS

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 -