title: Molecular modification of N-cadherin in response to synaptic activity.
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.
authors.affiliation: Program in Cell Adhesion, The Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: W
authors.initials: W
authors.lastname: Shan
authors.forename: G R
authors.initials: GR
authors.lastname: Phillips
authors.forename: K
authors.initials: K
authors.lastname: Arndt
authors.forename: O
authors.initials: O
authors.lastname: Bozdagi
authors.forename: L
authors.initials: L
authors.lastname: Shapiro
authors.forename: G W
authors.initials: GW
authors.lastname: Huntley
authors.forename: D L
authors.initials: DL
authors.lastname: Benson
authors.forename: D R
authors.initials: DR
authors.lastname: Colman
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers; D015820:Cadherins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000378:metabolism; D019281:Dimerization; D010450:Endopeptidases / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006168:Guinea Pigs; D006624:Hippocampus / Q000166:cytology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000032:analysis / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D010446:Peptide Fragments / Q000032:analysis; D011188:Potassium / Q000494:pharmacology; D011487:Protein Conformation; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000032:analysis / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013572:Synaptic Vesicles / Q000737:chemistry / Q000378:metabolism*; D016708:Synaptophysin / Q000032:analysis / Q000378:metabolism; D015534:Trans-Activators; D051176:beta Catenin
chemical_list: D015763:2-Amino-5-phosphonovalerate; D015415:Biomarkers; D015820:Cadherins; D003598:Cytoskeletal Proteins; D010450:Endopeptidases; D018691:Excitatory Amino Acid Antagonists; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D010446:Peptide Fragments; D011188:Potassium; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D016708:Synaptophysin; D015534:Trans-Activators; D051176:beta Catenin; C495267:CTNNB1 protein, mouse; C495268:Ctnnb1 protein, rat; C033652:postsynaptic density proteins