title: Synaptic PRG-1 modulates excitatory transmission via lipid phosphate-mediated signaling.
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.
authors.affiliation: Institute of Cell Biology and Neurobiology and NeuroCure, Charité, Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Trimbuch
authors.forename: Prateep
authors.initials: P
authors.lastname: Beed
authors.forename: Johannes
authors.initials: J
authors.lastname: Vogt
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schuchmann
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Maier
authors.forename: Michael
authors.initials: M
authors.lastname: Kintscher
authors.forename: Jörg
authors.initials: J
authors.lastname: Breustedt
authors.forename: Markus
authors.initials: M
authors.lastname: Schuelke
authors.forename: Nora
authors.initials: N
authors.lastname: Streu
authors.forename: Olga
authors.initials: O
authors.lastname: Kieselmann
authors.forename: Irene
authors.initials: I
authors.lastname: Brunk
authors.forename: Gregor
authors.initials: G
authors.lastname: Laube
authors.forename: Ulf
authors.initials: U
authors.lastname: Strauss
authors.forename: Arne
authors.initials: A
authors.lastname: Battefeld
authors.forename: Hagen
authors.initials: H
authors.lastname: Wende
authors.forename: Carmen
authors.initials: C
authors.lastname: Birchmeier
authors.forename: Stefan
authors.initials: S
authors.lastname: Wiese
authors.forename: Michael
authors.initials: M
authors.lastname: Sendtner
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawabe
authors.forename: Mika
authors.initials: M
authors.lastname: Kishimoto-Suga
authors.forename: Nils
authors.initials: N
authors.lastname: Brose
authors.forename: Jan
authors.initials: J
authors.lastname: Baumgart
authors.forename: Beate
authors.initials: B
authors.lastname: Geist
authors.forename: Junken
authors.initials: J
authors.lastname: Aoki
authors.forename: Nic E
authors.initials: NE
authors.lastname: Savaskan
authors.forename: Anja U
authors.initials: AU
authors.lastname: Bräuer
authors.forename: Jerold
authors.initials: J
authors.lastname: Chun
authors.forename: Olaf
authors.initials: O
authors.lastname: Ninnemann
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schmitz
authors.forename: Robert
authors.initials: R
authors.lastname: Nitsch
mesh_terms: D000818:Animals; D004569:Electroencephalography; D006624:Hippocampus / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011509:Proteoglycans / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D018091:Receptors, AMPA / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D008246:Lysophospholipids; D011509:Proteoglycans; D018091:Receptors, AMPA; D049368:Receptors, Lysophosphatidic Acid; D033921:Vesicular Transport Proteins; C075430:serglycin; C104722:glutamate receptor ionotropic, AMPA 2; C032881:lysophosphatidic acid