Abstract
The relationship between adhesive interactions across the synaptic cleft and synaptic function has remained elusive. At certain CNS synapses, pre- to postsynaptic adhesion is mediated at least in part by neural (N-) cadherin. Here, we demonstrate that upon depolarization of hippocampal neurons in culture by K+ treatment, or application of NMDA or alpha-latrotoxin, synaptic N-cadherin dimerizes and becomes markedly protease resistant. These properties are indices of strong, stable, enhanced cadherin-mediated intercellular adhesion. N-cadherin retained protease resistance for at least 2 hr after recovery, while other surface molecules, including other cadherins, were completely degraded. The acquisition of protease resistance and dimerization of N-cadherin is not dependent on new protein synthesis, nor is it accompanied by internalization of N-cadherin. By immunocytochemistry, we found that high K+ selectively induces surface dispersion of N-cadherin, which, after recovery, returns to synaptic puncta. N-cadherin dispersion under K+ treatment parallels the rapid expansion of the presynaptic membrane consequent to the massive vesicle fusion that occurs with this type of depolarization. In contrast, with NMDA application, N-cadherin does not disperse but does acquire enhanced protease resistance and dimerizes. Our data strongly suggest that synaptic adhesion is dynamically and locally controlled, and modulated by synaptic activity.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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2-Amino-5-phosphonovalerate / pharmacology
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Animals
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Biomarkers
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Cadherins / analysis
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Cadherins / chemistry
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Cadherins / metabolism*
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Cells, Cultured
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Cytoskeletal Proteins / analysis
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Cytoskeletal Proteins / metabolism
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Dimerization
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Endopeptidases / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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Fluorescent Antibody Technique
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Guinea Pigs
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Hippocampus / cytology
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Mice
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Nerve Tissue Proteins / analysis
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Nerve Tissue Proteins / metabolism
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Neural Cell Adhesion Molecules / analysis
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Neural Cell Adhesion Molecules / metabolism
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Neurons / chemistry
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Neurons / cytology
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Neurons / metabolism*
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Peptide Fragments / analysis
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Potassium / pharmacology
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Protein Conformation
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Rabbits
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Rats
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Rats, Sprague-Dawley
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Receptors, AMPA / analysis
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Receptors, AMPA / metabolism
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Receptors, N-Methyl-D-Aspartate / analysis
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Receptors, N-Methyl-D-Aspartate / physiology
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology*
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Synaptic Vesicles / chemistry
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Synaptic Vesicles / metabolism*
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Synaptophysin / analysis
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Synaptophysin / metabolism
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Trans-Activators*
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beta Catenin
Substances
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Biomarkers
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CTNNB1 protein, mouse
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Cadherins
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Ctnnb1 protein, rat
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Cytoskeletal Proteins
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Excitatory Amino Acid Antagonists
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Nerve Tissue Proteins
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Neural Cell Adhesion Molecules
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Peptide Fragments
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Receptors, AMPA
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Receptors, N-Methyl-D-Aspartate
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Synaptophysin
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Trans-Activators
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beta Catenin
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postsynaptic density proteins
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2-Amino-5-phosphonovalerate
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Endopeptidases
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Potassium
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glutamate receptor ionotropic, AMPA 1