TY  - JOUR
A1  - Liu, Xingfeng
A1  - Huai, Jisen
A1  - Endle, Heiko
A1  - Schlüter, Leslie
A1  - Fan, Wei
A1  - Li, Yunbo
A1  - Richers, Sebastian
A1  - Yurugi, Hajime
A1  - Rajalingam, Krishnaraj
A1  - Ji, Haichao
A1  - Cheng, Hong
A1  - Rister, Benjamin
A1  - Horta, Guilherme
A1  - Baumgart, Jan
A1  - Berger, Hendrik
A1  - Laube, Gregor
A1  - Schmitt, Ulrich
A1  - Schmeißer, Michael Joachim
A1  - Böckers, Tobias M.
A1  - Tenzer, Stefan
A1  - Vlachos, Andreas
A1  - Deller, Thomas
A1  - Nitsch, Robert
A1  - Vogt, Johannes
T1  - PRG-1 regulates synaptic plasticity via intracellular PP2A/β1-integrin signaling
T2  - Developmental cell
N2  - Alterations in dendritic spine numbers are linked to deficits in learning and memory. While we previously revealed that postsynaptic plasticity-related gene 1 (PRG-1) controls lysophosphatidic acid (LPA) signaling at glutamatergic synapses via presynaptic LPA receptors, we now show that PRG-1 also affects spine density and synaptic plasticity in a cell-autonomous fashion via protein phosphatase 2A (PP2A)/β1-integrin activation. PRG-1 deficiency reduces spine numbers and β1-integrin activation, alters long-term potentiation (LTP), and impairs spatial memory. The intracellular PRG-1 C terminus interacts in an LPA-dependent fashion with PP2A, thus modulating its phosphatase activity at the postsynaptic density. This results in recruitment of adhesome components src, paxillin, and talin to lipid rafts and ultimately in activation of β1-integrins. Consistent with these findings, activation of PP2A with FTY720 rescues defects in spine density and LTP of PRG-1-deficient animals. These results disclose a mechanism by which bioactive lipid signaling via PRG-1 could affect synaptic plasticity and memory formation.
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/44306
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-443062
SN  - 1878-1551
SN  - 1534-5807
N1  - This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
VL  - 38
IS  - 3
SP  - 275
EP  - 290
PB  - Cell Press ; Elsevier
CY  - Cambridge, Mass. ; New York, NY
ER  -