Matrix metalloproteinase-9 controls NMDA receptor surface diffusion through integrin beta1 signaling

J Neurosci. 2009 May 6;29(18):6007-12. doi: 10.1523/JNEUROSCI.5346-08.2009.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Cathepsin G
  • Cathepsins / pharmacology
  • Cells, Cultured
  • Embryo, Mammalian
  • Enzyme Inhibitors / pharmacology
  • Hippocampus / cytology
  • Integrin beta1 / metabolism*
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Matrix Metalloproteinase 9 / pharmacology
  • Microscopy, Confocal / methods
  • Mutation
  • Neurons / metabolism*
  • Protein Transport / drug effects
  • Protein Transport / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Serine Endopeptidases / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Statistics, Nonparametric

Substances

  • Enzyme Inhibitors
  • Integrin beta1
  • NR1 NMDA receptor
  • Receptors, N-Methyl-D-Aspartate
  • Cathepsins
  • Serine Endopeptidases
  • Cathepsin G
  • Ctsg protein, rat
  • Matrix Metalloproteinase 9