TRPC5 channel-Caveolin-1-eNOS signalplexes coordinate interplay between Ca<sup>2+</sup> and NO signals in endothelial cells
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- Sakaguchi Reiko
- Department of Engineering, Kyoto Univ iCeMS, Kyoto Univ
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- Takahashi Nobuaki
- Department of Engineering, Kyoto Univ Hakubi Project, Kyoto Univ
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- Yoshida Takashi
- Department of Engineering, Kyoto Univ Faculty of Pharmaceutical Sciences, Teikyo Heisei Univ
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- Ogawa Nozomi
- Department of Engineering, Kyoto Univ
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- Ueda Yoshifumi
- Department of Engineering, Kyoto Univ
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- Hamano Satoshi
- Department of Engineering, Kyoto Univ
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- Yamaguchi Kaori
- Department of Engineering, Kyoto Univ
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- Sawamura Seishiro
- Department of Engineering, Kyoto Univ
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- Yamamoto Shinichiro
- Department of Engineering, Kyoto Univ Faculty of Pharmaceutical Sciences, Teikyo Heisei Univ
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- Hara Yuji
- Department of Engineering, Kyoto Univ
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- Mori Masayuki
- Department of Engineering, Kyoto Univ
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- Furukawa Tetsushi
- Medical Research Institute, Tokyo Medical and Dental Univ
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- Shimizu Shunichi
- Faculty of Pharmaceutical Sciences, Teikyo Heisei Univ
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- Inoue Ryuji
- Department of Physiology, Fukuoka Univ.
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- Mori Yasuo
- Department of Engineering, Kyoto Univ iCeMS, Kyoto Univ
Bibliographic Information
- Other Title
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- TRPC5 チャネル-カベオリン-1-eNOS 複合体による血管内皮細胞におけるCa<sup>2+</sup> とNOシグナルの制御
Description
<p>The cell signaling molecules nitric oxide (NO) and Ca2+ regulate diverse biological processes through closely coordinated activities. However, signaling protein complexes that underlie the interplay between Ca2+ and NO pathways remain unclear in many tissues and cell types. Here we demonstrate the physical and functional interaction of the receptor-activated Ca2+-permeable TRPC5 channel with Ca2+-dependent endothelial NO synthase (eNOS) in vascular endothelial cells as well as HEK293 cells overexpressing these proteins. Upon stimulation of G-protein-coupled ATP receptors, Ca2+ influx via receptor-activated TRPC5 channels elicits NO production from eNOS, which in turn induces secondary activation of TRPC5 channels via cysteine S-nitrosylation. TRPC5 is co-immunoprecipitated with eNOS and the scaffolding protein caveolin-1. Mutations in the caveolin-1-binding domains of TRPC5 impair their association and disrupt Ca2+ influx and NO production, suggesting that caveolin-1 is the scaffold that enables TRPC5 and eNOS to assemble into the signaling complex. Interestingly, ATP receptor-activated Ca2+ influx dissociates eNOS from caveolin-1 but enhances the association between TRPC5 and eNOS at the plasma membrane. This may relieve eNOS from negative regulation by caveolin-1 and promote the production of NO in the vicinity of TRPC5, leading to an efficient secondary activation of TRPC5 via S-nitrosylation. Thus, our study provides evidence that the TRPC5 channel-cavolin-1-eNOS complex dynamically coordinates NO and Ca2+ signaling in vascular endothelial cells.</p>
Journal
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- Proceedings for Annual Meeting of The Japanese Pharmacological Society
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Proceedings for Annual Meeting of The Japanese Pharmacological Society 94 (0), 3-Y-G2-1-, 2021
Japanese Pharmacological Society
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Keywords
Details 詳細情報について
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- CRID
- 1390568916163901696
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- NII Article ID
- 130008001798
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- ISSN
- 24354953
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- Text Lang
- ja
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- Data Source
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- JaLC
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed