Structural basis of PI(4,5)P2-dependent regulation of GluA1 by phosphatidylinositol-5-phosphate 4-kinase, type II, alpha (PIP5K2A)
| Autor: | Fabian Hertel, Michael Pusch, Eric Schulze-Bahr, Nathalie Strutz-Seebohm, Lutz Pott, Markus Dicks, Veronika Matschke, Jan Terhag, Guiscard Seebohm, Ina Rothenberg, Florian Lang, Michael Hollmann, Eva Wrobel, Oana N. Ursu, Raphael Stoll |
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| Rok vydání: | 2014 |
| Předmět: |
Phosphatidylinositol 4
5-Diphosphate Phosphatidylinositol-4 5-bisphosphate (PIP2) Physiology Xenopus Molecular Sequence Data Clinical Biochemistry AMPA receptor Biology 5-bisphosphate (PIP2) Physiology (medical) Animals Humans PIP2 binding Amino Acid Sequence Receptors AMPA Kinase activity Receptor Phosphatidylinositol 5-phosphate Alanine Binding Sites Phosphatidylinositol-4 Kinase HEK 293 cells Glutamate receptor Molecular biology Phosphotransferases (Alcohol Group Acceptor) HEK293 Cells Ion Channels Receptors and Transporters Protein Binding Regulation Ionotropic effect |
| Zdroj: | Pflügers Archiv 466 (2014): 1885–1897. doi:10.1007/s00424-013-1424-8 info:cnr-pdr/source/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/titolo:Structural basis of PI(4,5)P-2-dependent regulation of GluA1 by phosphatidylinositol-5-phosphate 4-kinase, type II, alpha (PIP5K2A)/doi:10.1007%2Fs00424-013-1424-8/rivista:Pflügers Archiv/anno:2014/pagina_da:1885/pagina_a:1897/intervallo_pagine:1885–1897/volume:466 Pflugers Archiv |
| ISSN: | 1432-2013 0031-6768 |
| Popis: | 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)P2, 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)P2 effect by performing an alanine scan that suggested PI(4,5)P2 binding to this area. A PIP strip assay revealed PI(4,5)P2 binding to the C-terminal GluA1 peptide. The present observations disclose a novel mechanism in the regulation of GluA1. Electronic supplementary material The online version of this article (doi:10.1007/s00424-013-1424-8) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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