Soluble N-cadherin stimulates fibroblast growth factor receptor dependent neurite outgrowth and N-cadherin and the fibroblast growth factor receptor co-cluster in cells.
A chimeric molecule consisting of the extracellular domain of the adhesion molecule, N-cadherin, fused to the Fc region of human IgG (NCAD-Fc) supports calcium-dependent cell adhesion and promotes neurite outgrowth following affinity-capture to a tissue culture substrate. When presented to cerebellar neurons as a soluble molecule, the NCAD-Fc stimulated neurite outgrowth in a manner equivalent to that seen for N-cadherin expressed as a cell surface glycoprotein. Neurons expressing a dominant-negative version of the fibroblast growth factor (FGF) receptor did not respond to soluble NCAD-Fc. In cells transfected with full-length N-cadherin and the FGF receptor, antibody-clustering of N-cadherin resulted in a co-clustering of the FGF receptor to discrete patches in the cell membrane. The data demonstrate that the ability of N-cadherin to stimulate neurite outgrowth can be dissociated from its ability to function as a substrate associated adhesion molecule. The N-cadherin and the FGF receptor co-clustering in cells provides a basis for the neurite outgrowth response stimulated by N-cadherin being dependent on FGF receptor function.
Molecular Neurobiology Group, GKT School of Medicine, London, UK. m.utton@iop.kcl.ac.uk
M A
MA
Utton
B
B
Eickholt
F V
FV
Howell
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J
Wallis
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P
Doherty
D016475:3T3 Cells; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D002531:Cerebellum / Q000166:cytology / Q000502:physiology; D002642:Chick Embryo; D002645:Chickens; D003001:Cloning, Molecular; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D014168:Transferrin / Q000494:pharmacology
D015820:Cadherins; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; D014168:Transferrin; C496348:FGFR1 protein, human; C496349:Fgfr1 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1