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-Suga, Nils Brose, Jan Baumgart, Beate Geist, Junken Aoki, Nic E. Savaskan, Anja U. Bräuer, Jerold Chun, Olaf Ninnemann, Dietmar Schmitz, Robert Nitsch
Cell. 2009-09-01; 138(6): 1222-1235
DOI: 10.1016/j.cell.2009.06.050

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1. Cell. 2009 Sep 18;138(6):1222-35. doi: 10.1016/j.cell.2009.06.050.

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

Trimbuch T(1), 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 NE, Bräuer AU, Chun J, Ninnemann O, Schmitz
D, Nitsch R.

Author information:
(1)Institute of Cell Biology and Neurobiology and NeuroCure, Charité,
Universitätsmedizin Berlin, Berlin, Germany.

Erratum in
Cell. 2011 Sep 16;146(6):1043.

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.

DOI: 10.1016/j.cell.2009.06.050
PMCID: PMC3716297
PMID: 19766573 [Indexed for MEDLINE]

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