Author/Authors :
Thorsten Trimbuch، نويسنده , , Prateep Beed، نويسنده , , Johannes Vogt، نويسنده , , Sebastian Schuchmann، نويسنده , , Nikolaus Maier، نويسنده , , Michael Kintscher، نويسنده , , J?rg Breustedt، نويسنده , , Markus Schuelke، نويسنده , , Nora Streu، نويسنده , , Olga Kieselmann، نويسنده , , Irene Brunk، نويسنده , , Gregor Laube، نويسنده , , Ulf Strauss، نويسنده , , Arne Battefeld، نويسنده , , Hagen Wende، نويسنده , , Carmen Birchmeier، نويسنده , , Stefan Wiese، نويسنده , , Michael Sendtner، نويسنده , , Hiroshi Kawabe، نويسنده , , Mika Kishimoto-Suga، نويسنده , , et al.، نويسنده ,
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.
