Activity-dependent local translation of matrix metalloproteinase-9.
Local, synaptic synthesis of new proteins in response to neuronal stimulation plays a key role in the regulation of synaptic morphogenesis. Recent studies indicate that matrix metalloproteinase-9 (MMP-9), an endopeptidase that regulates the pericellular environment through cleavage of its protein components, plays a critical role in regulation of spine morphology and synaptic plasticity. Here, we sought to determine whether MMP-9 mRNA is transported to dendrites for local translation and protein release. First, dendritic transport of MMP-9 mRNA was seen in primary hippocampal neuronal cultures treated with glutamate and in dentate gyrus granule cells in adult anesthetized rats after induction of long-term potentiation. Second, rapid, activity-dependent polyadenylation of MMP-9 mRNA; association of the mRNA with actively translating polysomes; and de novo MMP-9 protein synthesis were obtained in synaptoneurosomes isolated from rat hippocampus. Third, glutamate stimulation of cultured hippocampal neurons evoked a rapid (in minutes) increase in MMP-9 activity, as measured by cleavage of its native substrate, β-dystroglycan. This activity was reduced by the polyadenylation inhibitor, thus linking MMP-9 translation with protein function. In aggregate, our findings show that MMP-9 mRNA is transported to dendrites and locally translated and that the protein is released in an activity-dependent manner. Acting in concert with other dendritically synthesized proteins, locally secreted MMP-9 may contribute to the structural and functional plasticity of the activated synapses.
Laboratory of Neurobiology, The Nencki Institute, 02-093 Warsaw, Poland. stanczyk@nencki.gov.pl
Magdalena
M
Dziembowska
Jacek
J
Milek
Aleksandra
A
Janusz
Emilia
E
Rejmak
Ewelina
E
Romanowska
Tomasz
T
Gorkiewicz
Adrian
A
Tiron
Clive R
CR
Bramham
Leszek
L
Kaczmarek
D000818:Animals; D003712:Dendrites / Q000201:enzymology; D004789:Enzyme Activation / Q000235:genetics; D006624:Hippocampus / Q000201:enzymology* / Q000502:physiology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism*; D019580:Perforant Pathway / Q000166:cytology / Q000201:enzymology; D061251:Primary Cell Culture; D014176:Protein Biosynthesis / Q000502:physiology*; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000201:enzymology
D020780:Matrix Metalloproteinase 9