Abstract
Matrix metalloproteinase-9 (MMP-9) has emerged as a physiological regulator of NMDA receptor (NMDAR)-dependent synaptic plasticity and memory. The pathways by which MMP-9 affects NMDAR signaling remain, however, elusive. Using single quantum dot tracking, we demonstrate that MMP-9 enzymatic activity increases NR1-NMDAR surface trafficking but has no influence on AMPA receptor mobility. The mechanism of MMP-9 action on NMDAR is not mediated by change in overall extracellular matrix structure nor by direct cleavage of NMDAR subunits, but rather through an integrin beta1-dependent pathway. These findings describe a new target pathway for MMP-9 action in key physiological and pathological brain processes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Analysis of Variance
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Animals
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Cathepsin G
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Cathepsins / pharmacology
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Cells, Cultured
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Embryo, Mammalian
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Enzyme Inhibitors / pharmacology
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Hippocampus / cytology
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Integrin beta1 / metabolism*
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Matrix Metalloproteinase 9 / genetics
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Matrix Metalloproteinase 9 / metabolism*
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Matrix Metalloproteinase 9 / pharmacology
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Microscopy, Confocal / methods
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Mutation
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Neurons / metabolism*
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Protein Transport / drug effects
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Protein Transport / physiology
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Rats
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Rats, Sprague-Dawley
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Receptors, N-Methyl-D-Aspartate / metabolism*
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Serine Endopeptidases / pharmacology
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Statistics, Nonparametric
Substances
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Enzyme Inhibitors
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Integrin beta1
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NR1 NMDA receptor
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Receptors, N-Methyl-D-Aspartate
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Cathepsins
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Serine Endopeptidases
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Cathepsin G
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Ctsg protein, rat
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Matrix Metalloproteinase 9