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Updated: Jul 3, 2026
04:48
A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate
Published on: July 10, 2018
MMP-7 cleaves the NR1 NMDA receptor subunit and modifies NMDA receptor function
Arek Szklarczyk1, Osefame Ewaleifoh, Jean-Claude Beique
1Johns Hopkins University, Department of Neurology, Pathology Bldg. Rm. 625, 600 N. Wolfe St., Baltimore, MD 21287, USA.
Summary
Matrix metalloproteinases-7 (MMP-7) cleaves the NMDA receptor
Area of Science:
- Neuroscience
- Biochemistry
- Enzymology
Background:
- Matrix metalloproteinases (MMPs) are enzymes involved in inflammation and cancer.
- Emerging evidence links MMPs to brain development and neurodegenerative diseases.
- MMPs can degrade synaptic proteins crucial for neuronal function.
Purpose of the Study:
- To investigate the role of MMP-7 in synaptic function.
- To identify specific synaptic targets of MMP-7.
- To determine the functional consequences of MMP-7 activity on neuronal receptors.
Main Methods:
- Analysis of murine cortical slice extracts.
- Cleavage assays using recombinant MMP-7.
- Western blot analysis to detect receptor fragments.
- Measurement of NMDA-mediated calcium flux.
- Electrophysiological recordings to determine AMPA/NMDA ratio.
Main Results:
- MMP-7 cleaves the NR1 subunit of the NMDA receptor at amino acid 517.
- MMP-7 also cleaves the NR2A subunit but not select AMPA receptor subunits.
- MMP-7 pretreatment diminishes NMDA-mediated calcium flux.
- MMP-7 pretreatment increases the AMPA/NMDA ratio.
Conclusions:
- MMP-7 directly targets and cleaves key subunits of the NMDA receptor.
- MMP-7 activity alters synaptic transmission by affecting NMDA receptor function.
- Elevated MMP-7 levels may contribute to altered synaptic function in neurological disorders.
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