title: Matrix metalloproteinases regulate the formation of dendritic spine head protrusions during chemically induced long-term potentiation.
abstract: Dendritic spines are are small membranous protrusions that extend from neuronal dendrites and harbor the majority of excitatory synapses. Increasing evidence has shown that matrix metalloproteinases (MMPs), a family of extracellularly acting and Zn(2+)-dependent endopeptidases, are able to rapidly modulate dendritic spine morphology. Spine head protrusions (SHPs) are filopodia-like processes that extend from the dendritic spine head, representing a form of postsynaptic structural remodeling in response to altered neuronal activity. Herein, we show that chemically induced long-term potentiation (cLTP) in dissociated hippocampal cultures upregulates MMP-9 activity that controls the formation of SHPs. Blocking of MMPs activity or microtubule dynamics abolishes the emergence of SHPs. In addition, autoactive recombinant MMP-9, promotes the formation of SHPs in organotypic hippocampal slices. Furthermore, spines with SHPs gained postsynaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA) receptors upon cLTP and the synaptic delivery of AMPA receptors was controlled by MMPs. The present results strongly imply that MMP-9 is functionally involved in the formation of SHPs and the control of postsynaptic receptor distribution upon cLTP.
authors.affiliation: Department of Molecular and Cellular Neurobiology, The Nencki Institute of Experimental Biology, Warsaw, Poland.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Szepesi
authors.forename: Monika
authors.initials: M
authors.lastname: Bijata
authors.forename: Blazej
authors.initials: B
authors.lastname: Ruszczycki
authors.forename: Leszek
authors.initials: L
authors.lastname: Kaczmarek
authors.forename: Jakub
authors.initials: J
authors.lastname: Wlodarczyk
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism
chemical_list: D018091:Receptors, AMPA; D020782:Matrix Metalloproteinases; D020780:Matrix Metalloproteinase 9