Qa-SNARE syntaxin 18 mediates lipid droplet fusion with SNAP23 and SEC22B

Lipid droplets (LDs) are dynamic lipid storage organelles that can sense and respond to changes in systemic energy balance. The size and number of LDs are controlled by complex and delicate mechanisms, among which, whether and which SNARE proteins mediate LD fusion, and the mechanisms governing this...

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Autores principales: Fu, Yuhui, Ding, Binbin, Liu, Xiaoxia, Zhao, Shangang, Chen, Fang, Li, Linsen, Zhu, Yi, Zhao, Jingxuan, Yuan, Zhen, Shen, Yafeng, Yang, Chaofeng, Shao, Mengle, Chen, She, Bickel, Perry E., Zhong, Qing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Nature Singapore 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663520/
https://www.ncbi.nlm.nih.gov/pubmed/37989733
http://dx.doi.org/10.1038/s41421-023-00613-4
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author Fu, Yuhui
Ding, Binbin
Liu, Xiaoxia
Zhao, Shangang
Chen, Fang
Li, Linsen
Zhu, Yi
Zhao, Jingxuan
Yuan, Zhen
Shen, Yafeng
Yang, Chaofeng
Shao, Mengle
Chen, She
Bickel, Perry E.
Zhong, Qing
author_facet Fu, Yuhui
Ding, Binbin
Liu, Xiaoxia
Zhao, Shangang
Chen, Fang
Li, Linsen
Zhu, Yi
Zhao, Jingxuan
Yuan, Zhen
Shen, Yafeng
Yang, Chaofeng
Shao, Mengle
Chen, She
Bickel, Perry E.
Zhong, Qing
author_sort Fu, Yuhui
collection PubMed
description Lipid droplets (LDs) are dynamic lipid storage organelles that can sense and respond to changes in systemic energy balance. The size and number of LDs are controlled by complex and delicate mechanisms, among which, whether and which SNARE proteins mediate LD fusion, and the mechanisms governing this process remain poorly understood. Here we identified a SNARE complex, syntaxin 18 (STX18)–SNAP23–SEC22B, that is recruited to LDs to mediate LD fusion. STX18 targets LDs with its transmembrane domain spanning the phospholipid monolayer twice. STX18–SNAP23–SEC22B complex drives LD fusion in adiposome lipid mixing and content mixing in vitro assays. CIDEC/FSP27 directly binds STX18, SEC22B, and SNAP23, and promotes the lipid mixing of SNAREs-reconstituted adiposomes by promoting LD clustering. Knockdown of STX18 in mouse liver via AAV resulted in smaller liver and reduced LD size under high-fat diet conditions. All these results demonstrate a critical role of the SNARE complex STX18–SNAP23–SEC22B in LD fusion.
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spelling pubmed-106635202023-11-21 Qa-SNARE syntaxin 18 mediates lipid droplet fusion with SNAP23 and SEC22B Fu, Yuhui Ding, Binbin Liu, Xiaoxia Zhao, Shangang Chen, Fang Li, Linsen Zhu, Yi Zhao, Jingxuan Yuan, Zhen Shen, Yafeng Yang, Chaofeng Shao, Mengle Chen, She Bickel, Perry E. Zhong, Qing Cell Discov Article Lipid droplets (LDs) are dynamic lipid storage organelles that can sense and respond to changes in systemic energy balance. The size and number of LDs are controlled by complex and delicate mechanisms, among which, whether and which SNARE proteins mediate LD fusion, and the mechanisms governing this process remain poorly understood. Here we identified a SNARE complex, syntaxin 18 (STX18)–SNAP23–SEC22B, that is recruited to LDs to mediate LD fusion. STX18 targets LDs with its transmembrane domain spanning the phospholipid monolayer twice. STX18–SNAP23–SEC22B complex drives LD fusion in adiposome lipid mixing and content mixing in vitro assays. CIDEC/FSP27 directly binds STX18, SEC22B, and SNAP23, and promotes the lipid mixing of SNAREs-reconstituted adiposomes by promoting LD clustering. Knockdown of STX18 in mouse liver via AAV resulted in smaller liver and reduced LD size under high-fat diet conditions. All these results demonstrate a critical role of the SNARE complex STX18–SNAP23–SEC22B in LD fusion. Springer Nature Singapore 2023-11-21 /pmc/articles/PMC10663520/ /pubmed/37989733 http://dx.doi.org/10.1038/s41421-023-00613-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Fu, Yuhui
Ding, Binbin
Liu, Xiaoxia
Zhao, Shangang
Chen, Fang
Li, Linsen
Zhu, Yi
Zhao, Jingxuan
Yuan, Zhen
Shen, Yafeng
Yang, Chaofeng
Shao, Mengle
Chen, She
Bickel, Perry E.
Zhong, Qing
Qa-SNARE syntaxin 18 mediates lipid droplet fusion with SNAP23 and SEC22B
title Qa-SNARE syntaxin 18 mediates lipid droplet fusion with SNAP23 and SEC22B
title_full Qa-SNARE syntaxin 18 mediates lipid droplet fusion with SNAP23 and SEC22B
title_fullStr Qa-SNARE syntaxin 18 mediates lipid droplet fusion with SNAP23 and SEC22B
title_full_unstemmed Qa-SNARE syntaxin 18 mediates lipid droplet fusion with SNAP23 and SEC22B
title_short Qa-SNARE syntaxin 18 mediates lipid droplet fusion with SNAP23 and SEC22B
title_sort qa-snare syntaxin 18 mediates lipid droplet fusion with snap23 and sec22b
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663520/
https://www.ncbi.nlm.nih.gov/pubmed/37989733
http://dx.doi.org/10.1038/s41421-023-00613-4
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