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Synaptic PRG-1 modulates excitatory transmission via lipid phosphate-mediated signaling

Item Type:Article
Title:Synaptic PRG-1 modulates excitatory transmission via lipid phosphate-mediated signaling
Creators Name:Trimbuch, T. and Beed, P. and Vogt, J. and Schuchmann, S. and Maier, N. and Kintscher, M. and Breustedt, J. and Schuelke, M. and Streu, N. and Kieselmann, O. and Brunk, I. and Laube, G. and Strauss, U. and Battefeld, A. and Wende, H. and Birchmeier, C. and Wiese, S. and Sendtner, M. and Kawabe, H. and Kishimoto-Suga, M. and Brose, N. and Baumgart, J. and Geist, B. and Aoki, J. and Savaskan, N.E. and Braeuer, A.U. and Chun, J. and Ninnemann, O. and Schmitz, D. and Nitsch, R.
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.
Keywords:MOLNEURO, Electroencephalography, Hippocampus, Lysophospholipids, Proteoglycans, AMPA Receptors, Lysophosphatidic Acid Receptors, Signal Transduction, Synapses, Vesicular Transport Proteins, Animals, Mice
Source:Cell
ISSN:0092-8674
Publisher:Cell Press (U.S.A.)
Volume:138
Number:6
Page Range:1222-12235
Date:18 September 2009
Additional Information:Erratum in: Cell. 2011 Sep 16;146(6):1043.
Official Publication:https://doi.org/10.1016/j.cell.2009.06.050
PubMed:View item in PubMed

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