Matrix metalloproteinase-9 controls NMDA receptor surface diffusion through integrin beta1 signaling.
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.
The Nencki Institute, 02-093 Warsaw, Poland.
Piotr
P
Michaluk
Lenka
L
Mikasova
Laurent
L
Groc
Renato
R
Frischknecht
Daniel
D
Choquet
Leszek
L
Kaczmarek
D000704:Analysis of Variance; D000818:Animals; D056649:Cathepsin G; D002403:Cathepsins / Q000494:pharmacology; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D019012:Integrin beta1 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D018613:Microscopy, Confocal / Q000379:methods; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D018709:Statistics, Nonparametric
D004791:Enzyme Inhibitors; D019012:Integrin beta1; C409466:NR1 NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D002403:Cathepsins; D012697:Serine Endopeptidases; D056649:Cathepsin G; C534097:Ctsg protein, rat; D020780:Matrix Metalloproteinase 9