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

Thorsten Trimbuch, Prateep Beed, Johannes Vogt, Sebastian Schuchmann, Nikolaus Maier, Michael Kintscher, Jörg Breustedt, Markus Schuelke, Nora Streu, Olga Kieselmann, Irene Brunk, Gregor Laube, Ulf Strauss, Arne Battefeld, Hagen Wende, Carmen Birchmeier, Stefan Wiese, Michael Sendtner, Hiroshi Kawabe, Mika Kishimoto-SugaNils Brose, Jan Baumgart, Beate Geist, Junken Aoki, Nic E. Savaskan, Anja U. Bräuer, Jerold Chun, Olaf Ninnemann, Dietmar Schmitz, Robert Nitsch

Research output: Contribution to journalArticlepeer-review

86 Citations (Scopus)

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 LPA2 receptor-deficient animals, and uptake of phospholipids is reduced in PRG-1-deficient neurons, we assessed PRG-1/LPA2 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 LPA2 receptor signaling.

Original languageEnglish
Pages (from-to)1222-1235
Number of pages14
JournalCell
Volume138
Issue number6
DOIs
Publication statusPublished - 2009 Sep 18

Keywords

  • MOLNEURO

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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