| First Author | Trimbuch T | Year | 2009 |
| Journal | Cell | Volume | 138 |
| Issue | 6 | Pages | 1222-35 |
| PubMed ID | 19766573 | Mgi Jnum | J:157318 |
| Mgi Id | MGI:4430657 | Doi | 10.1016/j.cell.2009.06.050 |
| Citation | Trimbuch T, et al. (2009) Synaptic PRG-1 modulates excitatory transmission via lipid phosphate-mediated signaling. Cell 138(6):1222-35 |
| abstractText | 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. |
