Synaptic PRG-1 modulates excitatory transmission via lipid phosphate-mediated signaling.
Cell. 2009-09-01; 138(6): 1222-1235
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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.
(1)Institute of Cell Biology and Neurobiology and NeuroCure, Charité,
Universitätsmedizin Berlin, Berlin, Germany.
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.
PMID: 19766573 [Indexed for MEDLINE]