Xingfeng Liu, Jisen Huai, Heiko Endle, Leslie Schlüter, Wei Fan, Yunbo Li, Sebastian Richers, Hajime Yurugi, Krishnaraj Rajalingam, Haichao Ji, Hong Cheng, Benjamin Rister, Guilherme Horta, Jan Baumgart, Hendrik Berger, Gregor Laube, Ulrich Schmitt, Michael Joachim Schmeißer, Tobias M. Böckers, Stefan Tenzer, Andreas Vlachos, Thomas Deller, Robert Nitsch, Johannes Vogt
- 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.
MetadatenAuthor: | Xingfeng Liu, Jisen Huai, Heiko EndleORCiD, Leslie Schlüter, Wei Fan, Yunbo Li, Sebastian Richers, Hajime Yurugi, Krishnaraj RajalingamORCiDGND, Haichao Ji, Hong Cheng, Benjamin Rister, Guilherme Horta, Jan Baumgart, Hendrik Berger, Gregor Laube, Ulrich Schmitt, Michael Joachim Schmeißer, Tobias M. Böckers, Stefan TenzerORCiDGND, Andreas VlachosORCiDGND, Thomas DellerORCiDGND, Robert NitschGND, Johannes VogtORCiD |
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URN: | urn:nbn:de:hebis:30:3-443062 |
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DOI: | https://doi.org/10.1016/j.devcel.2016.06.019 |
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ISSN: | 1878-1551 |
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ISSN: | 1534-5807 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/27453502 |
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Parent Title (English): | Developmental cell |
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Publisher: | Cell Press ; Elsevier |
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Place of publication: | Cambridge, Mass. ; New York, NY |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2017/06/26 |
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Year of first Publication: | 2016 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2017/06/26 |
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Volume: | 38 |
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Issue: | 3 |
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Page Number: | 17 |
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First Page: | 275 |
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Last Page: | 290 |
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Note: | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
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HeBIS-PPN: | 428710344 |
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Institutes: | Medizin / Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung 4.0 |
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