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| Item Type: | Article |
|---|---|
| Title: | Synaptic PRG-1 modulates excitatory transmission via lipid phosphate-mediated signaling |
| Creators: |
Trimbuch, T.  ORCID: https://orcid.org/0000-0001-7512-8955, Beed, P., Vogt, J., Schuchmann, S., Maier, N., Kintscher, M., Breustedt, J., Schuelke, M., Streu, N., Kieselmann, O., Brunk, I., Laube, G., Strauss, U., Battefeld, A., Wende, H. ORCID: https://orcid.org/0000-0002-9168-8095, Birchmeier, C. ORCID: https://orcid.org/0000-0002-2041-8872, Wiese, S., Sendtner, M., Kawabe, H., Kishimoto-Suga, M., Brose, N., Baumgart, J., Geist, B., Aoki, J., Savaskan, N.E., Braeuer, A.U., Chun, J., Ninnemann, O., Schmitz, D. ORCID: https://orcid.org/0000-0003-2741-5241 and Nitsch, R.
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| Abstract: | Plasticity related gene-1 (PRG-1) is a brain-specific membrane protein related to lipid phosphate phosphatases, which acts in the hippocampus specifically at the excitatory synapse terminating on glutamatergic neurons. Deletion of prg-1 in mice leads to epileptic seizures and augmentation of EPSCs, but not IPSCs. In utero electroporation of PRG-1 into deficient animals revealed that PRG-1 modulates excitation at the synaptic junction. Mutation of the extracellular domain of PRG-1 crucial for its interaction with lysophosphatidic acid (LPA) abolished the ability to prevent hyperexcitability. As LPA application in vitro induced hyperexcitability in wild-type but not in LPA(2) receptor-deficient animals, and uptake of phospholipids is reduced in PRG-1-deficient neurons, we assessed PRG-1/LPA(2) receptor-deficient animals, and found that the pathophysiology observed in the PRG-1-deficient mice was fully reverted. Thus, we propose PRG-1 as an important player in the modulatory control of hippocampal excitability dependent on presynaptic LPA(2) receptor signaling. |
| Keywords: | MOLNEURO, Electroencephalography, Hippocampus, Lysophospholipids, Proteoglycans, AMPA Receptors, Lysophosphatidic Acid Receptors, Signal Transduction, Synapses, Vesicular Transport Proteins, Animals, Mice |
| Source: | Cell |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Volume: | 138 |
| Number: | 6 |
| Page Range: | 1222-12235 |
| Date: | 18 September 2009 |
| Additional Information: | Erratum in: Cell. 2011 Sep 16;146(6):1043. |
| Official Publication: | https://doi.org/10.1016/j.cell.2009.06.050 |
| PubMed: | View item in PubMed |
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