Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Cell, 2009-09, Vol.138 (6), p.1222-1235

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2009

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.