Beta-dystroglycan As a Target for Mmp-9, in Response to Enhanced Neuronal Activity.
From: Department of Molecular and Cellular Neurobiology, Nencki Institute, Pasteura 3, 02-093 Warsaw, Poland.
The Journal of biological chemistry
- Publish Date: Jun 2007
- ISSN: 0021-9258
- Volume: 282
- Issue: 22
- Pages: 16036-41
- Medium: Print
- Language: English
- Citation (JAMA): Michaluk Piotr, Kolodziej Lukasz, Mioduszewska Barbara, et al. Beta-dystroglycan As a Target for Mmp-9, in Response to Enhanced Neuronal Activity.. J. Biol. Chem. Jun 2007;282:16036-41
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 beta-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 beta-dystroglycan. (ii) In neuronal cultures, beta-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) Beta-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) Beta-dystroglycan cleavage correlates in time with increased matrix metalloproteinase-9 activity. (v) Finally, beta-dystroglycan and matrix metalloproteinase-9 colocalize in postsynaptic elements in the hippocampus. In conclusion, our data identify the beta-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.
Mesh Headings (Keywords): Animals, Animals, Newborn, Bicuculline, Cells, Cultured, Dystroglycans, Enzyme Activation, GABA Antagonists, Glutamic Acid, Hippocampus, Matrix Metalloproteinase 9, Memory, Mice, Mice, Knockout, Neuronal Plasticity, Neurons, Rats, Rats, Wistar, Recombinant Proteins, Synapses, Tissue Inhibitor of Metalloproteinase-1
Check for Full Text / PubMed Unique Identifier (PMID): 17426029
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.