β-Dystroglycan as a target for MMP-9, in response to enhanced neuronal activity

P. Michaluk, L. Kolodziej, B. Mioduszewska, G. Wilczynski, J. Dzwonek, J. Jaworski, Darek Gorecki, O. Ottersen, L. Kaczmarek

Research output: Contribution to journalArticlepeer-review

Abstract

Matrix metalloproteinase-9 has recently emerged as an important molecule in control of extracellular proteolysis in the synaptic plasticity. However, no synaptic targets for its enzymatic activity had been identified before. In this report, we show that β-dystroglycan comprises such a neuronal activity-driven target for matrix metalloproteinase-9. This notion is based on the following observations. (i) Recombinant, autoactivating matrix metalloproteinase-9 produces limited proteolytic cleavage of β-dystroglycan. (ii) In neuronal cultures, β-dystroglycan proteolysis occurs in response to stimulation with either glutamate or bicuculline and is blocked by tissue inhibitor of metalloproteinases-1, a metalloproteinase inhibitor. (iii) β-Dystroglycan degradation is also observed in the hippocampus in vivo in response to seizures but not in the matrix metalloproteinase-9 knock-out mice. (iv) β-Dystroglycan cleavage correlates in time with increased matrix metalloproteinase-9 activity. (v) Finally, β-dystroglycan and matrix metalloproteinase-9 colocalize in postsynaptic elements in the hippocampus. In conclusion, our data identify the β-dystroglycan as a first matrix metalloproteinase-9 substrate digested in response to enhanced synaptic activity. This demonstration may help to understand the possible role of both proteins in neuronal functions, especially in synaptic plasticity, learning, and memory.
Original languageEnglish
Pages (from-to)16036-16041
Number of pages6
JournalThe Journal of Biological Chemistry
Volume282
Issue number22
DOIs
Publication statusPublished - 1 Jun 2007

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