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Elsevier, Cell, 6(146), p. 1043, 2011

DOI: 10.1016/j.cell.2011.08.029

Elsevier, Cell, 6(138), p. 1222-1235, 2009

DOI: 10.1016/j.cell.2009.06.050

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Synaptic PRG-1 Modulates Excitatory Transmission via Lipid Phosphate-Mediated Signaling

Journal article published in 2009 by Thorsten Trimbuch, Prateep Beed, Johannes Vogt ORCID, Sebastian Schuchmann, Michael Kintscher, Nikolaus Maier ORCID, Jörg Breustedt, Markus Schuelke, Nora Streu, Olga Kieselmann, Irene Brunk, Gregor Laube, Ulf Strauss, Arne Battefeld, Hagen Wende and other authors.
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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.