Abstract
N-Cadherin has an important role during dendrite arborization, axon guidance, and synaptogenesis. In particular, at synaptic sites, N-cadherin is involved in the regulation of cell-cell adhesion and in morphology and plasticity control. Recent studies have shown that N-cadherin can be cleaved by the metalloproteinase ADAM10. Here we demonstrate that impairing ADAM10 localization and activity at synaptic sites decreases its processing of N-cadherin. This leads to an accumulation of the full-length form of N-cadherin, to an increase in spine head width, and to modifications of the number and function of glutamate receptors of AMPA type, both in vitro and in vivo. Our results indicate a key role for ADAM10 in the complex sequence of events through which N-cadherin affects spine maturation and controls structure and function of glutamatergic synapses.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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ADAM Proteins / analysis
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ADAM Proteins / physiology*
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ADAM10 Protein
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Amino Acid Sequence
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Amyloid Precursor Protein Secretases / analysis
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Amyloid Precursor Protein Secretases / physiology*
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Animals
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Antigens, CD / physiology*
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Cadherins / physiology*
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Cells, Cultured
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Excitatory Postsynaptic Potentials / physiology*
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Glutamic Acid / chemistry
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Glutamic Acid / physiology
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Hippocampus / chemistry
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Hippocampus / metabolism
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Hippocampus / physiology
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Humans
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Membrane Proteins / analysis
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Membrane Proteins / physiology*
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Mice
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Molecular Sequence Data
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Rats
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Synapses / chemistry
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Synapses / metabolism*
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Synapses / physiology
Substances
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Antigens, CD
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CDH2 protein, human
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Cadherins
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Membrane Proteins
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Glutamic Acid
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Amyloid Precursor Protein Secretases
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ADAM Proteins
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ADAM10 Protein
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ADAM10 protein, human