http://www.cnr.it/ontology/cnr/individuo/prodotto/ID286798
Structural basis of PI(4,5)P-2-dependent regulation of GluA1 by phosphatidylinositol-5-phosphate 4-kinase, type II, alpha (PIP5K2A) (Articolo in rivista)
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- Structural basis of PI(4,5)P-2-dependent regulation of GluA1 by phosphatidylinositol-5-phosphate 4-kinase, type II, alpha (PIP5K2A) (Articolo in rivista) (literal)
- Anno
- 2014-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.1007/s00424-013-1424-8 (literal)
- Alternative label
Seebohm, Guiscard; Wrobel, Eva; Pusch, Michael; Dicks, Markus; Terhag, Jan; Matschke, Veronika; Rothenberg, Ina; Ursu, Oana N.; Hertel, Fabian; Pott, Lutz; Lang, Florian; Schulze-Bahr, Eric; Hollmann, Michael; Stoll, Raphael; Strutz-Seebohm, Nathalie (2014)
Structural basis of PI(4,5)P-2-dependent regulation of GluA1 by phosphatidylinositol-5-phosphate 4-kinase, type II, alpha (PIP5K2A)
in Pflügers Archiv
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- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Seebohm, Guiscard; Wrobel, Eva; Pusch, Michael; Dicks, Markus; Terhag, Jan; Matschke, Veronika; Rothenberg, Ina; Ursu, Oana N.; Hertel, Fabian; Pott, Lutz; Lang, Florian; Schulze-Bahr, Eric; Hollmann, Michael; Stoll, Raphael; Strutz-Seebohm, Nathalie (literal)
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- University of Munster; Ist Biofis CNR; Ruhr University Bochum; Ruhr University Bochum; Eberhard Karls University of Tubingen; Ruhr University Bochum; Eberhard Karls University of Tubingen; University of Munster (literal)
- Titolo
- Structural basis of PI(4,5)P-2-dependent regulation of GluA1 by phosphatidylinositol-5-phosphate 4-kinase, type II, alpha (PIP5K2A) (literal)
- Abstract
- Ionotropic glutamate receptors are the most important excitatory receptors in the central nervous system, and their impairment can lead to multiple neuronal diseases. Here, we show that glutamate-induced currents in oocytes expressing GluA1 are increased by coexpression of the schizophrenia-associated phosphoinositide kinase PIP5K2A. This effect was due to enhanced membrane abundance and was blunted by a point mutation (N251S) in PIP5K2A. An increase in GluA1 currents was also observed upon acute injection of PI(4,5)P-2, the main product of PIP5K2A. By expression of wild-type and mutant PIP5K2A in human embryonic kidney cells, we were able to provide evidence of impaired kinase activity of the mutant PIP5K2A. We defined the region K813-K823 of GluA1 as critical for the PI(4,5)P-2 effect by performing an alanine scan that suggested PI(4,5)P-2 binding to this area. A PIP strip assay revealed PI(4,5)P-2 binding to the C-terminal GluA1 peptide. The present observations disclose a novel mechanism in the regulation of GluA1. (literal)
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