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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Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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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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