Helmholtz Gemeinschaft


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., Beed, P., Vogt, J., Schuchmann, S., Maier, N., Kintscher, M., Breustedt, J., Schuelke, M., Streu, N., Kieselmann, O., Brunk, I., Laube, G., Strauss, U., Battefeld, A., Wende, H., Birchmeier, C., Wiese, S., Sendtner, M., Kawabe, H., Kishimoto-Suga, M., Brose, N., Baumgart, J., Geist, B., Aoki, J., Savaskan, N.E., Braeuer, A.U., Chun, J., Ninnemann, O., 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
Publisher:Cell Press
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

Repository Staff Only: item control page

Open Access
MDC Library