Activity-Dependent Shedding of the NMDA Receptor Glycine Binding Site by Matrix Metalloproteinase 3: A PUTATIVE Mechanism of Postsynaptic Plasticity NR1 Shedding by MMP-3
2008

MMP-3 and NMDA Receptor Shedding in Neurons

Sample size: 50 publication 10 minutes Evidence: moderate

Author Information

Author(s): Pauly Thorsten, Ratliff Miriam, Pietrowski Eweline, Neugebauer Rainer, Schlicksupp Andrea, Kirsch Joachim, Kuhse Jochen

Primary Institution: Department of Anatomy and Cellular Neurobiology, University of Ulm; Department of Anatomy and Cell Biology, University of Heidelberg

Hypothesis

Chronic NMDA receptor stimulation leads to the shedding of the NR1 subunit by MMP-3.

Conclusion

MMP-3 is involved in the activity-dependent alteration of NMDA receptor structure at postsynaptic sites.

Supporting Evidence

  • Chronic NMDA receptor stimulation leads to a significant loss of extracellular NR1 epitopes.
  • MMP-3 activity is required for the NMDA-induced loss of extracellular NR1-epitopes.
  • Blocking MMP-3 prevents the loss of NR1 S2-epitopes during NMDA treatment.
  • Two major MMP-3 cleavage sites were identified within the NR1 subunit.

Takeaway

When neurons are stimulated for a long time, a part of the NMDA receptor gets cut off, which might help the brain adapt and learn.

Methodology

Cultured rat spinal cord neurons were treated with NMDA and analyzed for changes in NR1 subunit expression using immunofluorescence microscopy.

Limitations

The study primarily focuses on cultured neurons, which may not fully represent in vivo conditions.

Participant Demographics

Cultured rat spinal cord neurons from embryonic stage 14.

Statistical Information

P-Value

p<0.001

Statistical Significance

p<0.001

Digital Object Identifier (DOI)

10.1371/journal.pone.0002681

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