Synaptically released matrix metalloproteinase activity in control of structural plasticity and the cell surface distribution of GluA1-AMPA receptors.
Synapses are particularly prone to dynamic alterations and thus play a major role in neuronal plasticity. Dynamic excitatory synapses are located at the membranous neuronal protrusions called dendritic spines. The ability to change synaptic connections involves both alterations at the morphological level and changes in postsynaptic receptor composition. We report that endogenous matrix metalloproteinase (MMP) activity promotes the structural and functional plasticity of local synapses by its effect on glutamate receptor mobility and content. We used live imaging of cultured hippocampal neurons and quantitative morphological analysis to show that chemical long-term potentiation (cLTP) induces the permanent enlargement of a subset of small dendritic spines in an MMP-dependent manner. We also used a superresolution microscopy approach and found that spine expansion induced by cLTP was accompanied by MMP-dependent immobilization and synaptic accumulation as well as the clustering of GluA1-containing AMPA receptors. Altogether, our results reveal novel molecular and cellular mechanisms of synaptic plasticity.
Department of Molecular and Cellular Neurobiology, Nencki Institute, Warsaw, Poland.
Zsuzsanna
Z
Szepesi
Dynamic Organization and Function of Synapses, Interdisciplinary Institute for Neuroscience, Bordeaux, France.
Eric
E
Hosy
Department of Molecular and Cellular Neurobiology, Nencki Institute, Warsaw, Poland.
Blazej
B
Ruszczycki
Department of Molecular and Cellular Neurobiology, Nencki Institute, Warsaw, Poland.
Monika
M
Bijata
Department of Molecular and Cellular Neurobiology, Nencki Institute, Warsaw, Poland.
Marta
M
Pyskaty
Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany.
Arthur
A
Bikbaev
Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany.
Martin
M
Heine
Dynamic Organization and Function of Synapses, Interdisciplinary Institute for Neuroscience, Bordeaux, France.
Daniel
D
Choquet
Department of Molecular and Cellular Neurobiology, Nencki Institute, Warsaw, Poland.
Leszek
L
Kaczmarek
Department of Molecular and Cellular Neurobiology, Nencki Institute, Warsaw, Poland.
Jakub
J
Wlodarczyk
D000328:Adult; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009473:Neuronal Plasticity; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000201:enzymology*
D020782:Matrix Metalloproteinases; D018091:Receptors, AMPA