PRG-1 regulates synaptic plasticity via intracellular PP2A/β1-integrin signaling

Autor: Ulrich Schmitt, Johannes Vogt, Hong Cheng, Sebastian Richers, Benjamin Rister, Xingfeng Liu, Gregor Laube, Tobias M. Boeckers, Haichao Ji, Thomas Deller, Jan Baumgart, Hendrik Berger, Heiko Endle, Jisen Huai, Andreas Vlachos, Robert Nitsch, Michael J. Schmeisser, Leslie Schlüter, Krishnaraj Rajalingam, Yunbo Li, Wei Fan, Hajime Yurugi, Guilherme Horta, Stefan Tenzer
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
musculoskeletal diseases
Dendritic spine
Dendritic Spines
Long-Term Potentiation
Nonsynaptic plasticity
Biology
Hippocampus
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Membrane Microdomains
Postsynaptic potential
Lysophosphatidic acid
Animals
Guanine Nucleotide Exchange Factors
Protein Phosphatase 2
ddc:610
Molecular Biology
Cells
Cultured
Mice
Knockout
Focal Adhesions
Neuronal Plasticity
Adhesome
Integrin beta1
Long-term potentiation
Cell Biology
musculoskeletal system
Cell biology
030104 developmental biology
chemistry
Synaptic plasticity
Synapses
Lysophospholipids
Postsynaptic density
030217 neurology & neurosurgery
Rho Guanine Nucleotide Exchange Factors
Signal Transduction
Developmental Biology
Popis: SummaryAlterations 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.
Databáze: OpenAIRE
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