Cysteine 893 is a target of regulatory thiol modifications of GluA1 AMPA receptors.

Recent studies indicate that glutamatergic signaling involves, and is regulated by, thiol modifying and redox-active compounds. In this study, we examined the role of a reactive cysteine residue, Cys-893, in the cytosolic C-terminal tail of GluA1 AMPA receptor as a potential regulatory target. Elimi...

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Main Authors: Lotta von Ossowski, Li-Li Li, Tommi Möykkynen, Sarah K Coleman, Michael J Courtney, Kari Keinänen
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171489&type=printable
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author Lotta von Ossowski
Li-Li Li
Tommi Möykkynen
Sarah K Coleman
Michael J Courtney
Kari Keinänen
author_facet Lotta von Ossowski
Li-Li Li
Tommi Möykkynen
Sarah K Coleman
Michael J Courtney
Kari Keinänen
author_sort Lotta von Ossowski
collection DOAJ
description Recent studies indicate that glutamatergic signaling involves, and is regulated by, thiol modifying and redox-active compounds. In this study, we examined the role of a reactive cysteine residue, Cys-893, in the cytosolic C-terminal tail of GluA1 AMPA receptor as a potential regulatory target. Elimination of the thiol function by substitution of serine for Cys-893 led to increased steady-state expression level and strongly reduced interaction with SAP97, a major cytosolic interaction partner of GluA1 C-terminus. Moreover, we found that of the three cysteine residues in GluA1 C-terminal tail, Cys-893 is the predominant target for S-nitrosylation induced by exogenous nitric oxide donors in cultured cells and lysates. Co-precipitation experiments provided evidence for native association of SAP97 with neuronal nitric oxide synthase (nNOS) and for the potential coupling of Ca2+-permeable GluA1 receptors with nNOS via SAP97. Our results show that Cys-893 can serve as a molecular target for regulatory thiol modifications of GluA1 receptors, including the effects of nitric oxide.
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spelling doaj.art-d16e228ebfcf4fdc98c3e3457bebed372025-02-27T05:33:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01122e017148910.1371/journal.pone.0171489Cysteine 893 is a target of regulatory thiol modifications of GluA1 AMPA receptors.Lotta von OssowskiLi-Li LiTommi MöykkynenSarah K ColemanMichael J CourtneyKari KeinänenRecent studies indicate that glutamatergic signaling involves, and is regulated by, thiol modifying and redox-active compounds. In this study, we examined the role of a reactive cysteine residue, Cys-893, in the cytosolic C-terminal tail of GluA1 AMPA receptor as a potential regulatory target. Elimination of the thiol function by substitution of serine for Cys-893 led to increased steady-state expression level and strongly reduced interaction with SAP97, a major cytosolic interaction partner of GluA1 C-terminus. Moreover, we found that of the three cysteine residues in GluA1 C-terminal tail, Cys-893 is the predominant target for S-nitrosylation induced by exogenous nitric oxide donors in cultured cells and lysates. Co-precipitation experiments provided evidence for native association of SAP97 with neuronal nitric oxide synthase (nNOS) and for the potential coupling of Ca2+-permeable GluA1 receptors with nNOS via SAP97. Our results show that Cys-893 can serve as a molecular target for regulatory thiol modifications of GluA1 receptors, including the effects of nitric oxide.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171489&type=printable
spellingShingle Lotta von Ossowski
Li-Li Li
Tommi Möykkynen
Sarah K Coleman
Michael J Courtney
Kari Keinänen
Cysteine 893 is a target of regulatory thiol modifications of GluA1 AMPA receptors.
PLoS ONE
title Cysteine 893 is a target of regulatory thiol modifications of GluA1 AMPA receptors.
title_full Cysteine 893 is a target of regulatory thiol modifications of GluA1 AMPA receptors.
title_fullStr Cysteine 893 is a target of regulatory thiol modifications of GluA1 AMPA receptors.
title_full_unstemmed Cysteine 893 is a target of regulatory thiol modifications of GluA1 AMPA receptors.
title_short Cysteine 893 is a target of regulatory thiol modifications of GluA1 AMPA receptors.
title_sort cysteine 893 is a target of regulatory thiol modifications of glua1 ampa receptors
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171489&type=printable
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