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Redox-modulated SNX25 as a novel regulator of GPCR-G protein signaling from endosomes.

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العنوان: Redox-modulated SNX25 as a novel regulator of GPCR-G protein signaling from endosomes.
المؤلفون: Zhang Y; State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China; University of Chinese Academy of Sciences, Beijing, 100049, China., Yu Z; State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China., Sun M; Basic Research Center, Bioland Laboratory, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 510530, China., Du R; State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China; University of Chinese Academy of Sciences, Beijing, 100049, China., Gao H; State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China; University of Chinese Academy of Sciences, Beijing, 100049, China., Dai Q; State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China; University of Chinese Academy of Sciences, Beijing, 100049, China., Dong Y; State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China; Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China; China-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou, 510530, China., Liu C; Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China., Yin M; State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China; University of Chinese Academy of Sciences, Beijing, 100049, China., Xu T; State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China; Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China; China-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou, 510530, China., Zhang X; Basic Research Center, Bioland Laboratory, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 510530, China; CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Center for Cell Lineage and Development, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, 510530, China., Liu J; State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China; University of Chinese Academy of Sciences, Beijing, 100049, China; Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China; China-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou, 510530, China. Electronic address: liu_jinsong@gibh.ac.cn., Xu J; State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China; University of Chinese Academy of Sciences, Beijing, 100049, China; Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China; China-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou, 510530, China. Electronic address: xu_jinxin@gibh.ac.cn.
المصدر: Redox biology [Redox Biol] 2024 Sep; Vol. 75, pp. 103253. Date of Electronic Publication: 2024 Jun 22.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier, B.V Country of Publication: Netherlands NLM ID: 101605639 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2213-2317 (Electronic) Linking ISSN: 22132317 NLM ISO Abbreviation: Redox Biol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Amsterdam]: Elsevier, B.V., [2013]-
مواضيع طبية MeSH: Endosomes*/metabolism , Sorting Nexins*/metabolism , Sorting Nexins*/genetics , Signal Transduction* , Oxidation-Reduction* , RGS Proteins*/metabolism , RGS Proteins*/genetics , Receptors, G-Protein-Coupled*/metabolism, Humans ; Protein Binding
مستخلص: GPCR-G protein signaling from endosomes plays a crucial role in various physiological and pathological processes. However, the mechanism by which endosomal G protein signaling is terminated remains largely unknown. In this study, we aimed to investigate the regulatory mechanisms involved in terminating the signaling of Gα subunits from endosomes. Through structural analysis and cell-based assays, we have discovered that SNX25, a protein that targets endosomes via its PXA or PXC domain, interacts with regulator of G protein signaling (RGS) proteins (including RGS2, RGS4, RGS8, and RGS17) in a redox-regulated manner. The interaction between SNX25 and these RGS proteins enhances their GTPase-accelerating activity towards Gα i/q and their ability to bind GDP-bound (inactive form) Gα i/q . As a result, SNX25 recruits these RGS proteins to endosomes, leading to the termination of endosomal Gα i/q signaling. Furthermore, we have found that the SNX25/RGS complex also exerts a negative regulatory effect on Gα i/q signaling from the plasma membrane. This is achieved by recruiting Gα i/q to endosomes and preventing its activation on the plasma membrane. Our findings shed light on the previously unknown role of redox-modulated SNX25 in inhibiting Gα i/q signaling, thereby uncovering a novel mechanism for terminating Gα i/q signaling from endosomes. Importantly, this study expands our understanding of the regulation of GPCR-Gα i/q signaling beyond the plasma membrane.
Competing Interests: Declaration of competing interest The authors declare no competing interests.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Endosomal signaling; G-protein; GPCR; Redox; Regulator of G protein signaling (RGS); Sorting nexins (SNXs)
المشرفين على المادة: 0 (Sorting Nexins)
0 (RGS Proteins)
0 (Receptors, G-Protein-Coupled)
تواريخ الأحداث: Date Created: 20240627 Date Completed: 20240821 Latest Revision: 20240821
رمز التحديث: 20240822
مُعرف محوري في PubMed: PMC11259961
DOI: 10.1016/j.redox.2024.103253
PMID: 38936254
قاعدة البيانات: MEDLINE
الوصف
تدمد:2213-2317
DOI:10.1016/j.redox.2024.103253