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

Authors: FU, YUHUI - Shanghai Jiaotong University; DING, BINBIN - Huazhong University Of Science And Technology; LIU, XIAOXIA - Shanghai Jiaotong University; ZHAO, SHANGANG - University Of Texas At San Antonio; CHEN, FANG - Shanghai Jiaotong University; LI, LINSEN - Shanghai Jiaotong University; ZHU, YI - Children'S Nutrition Research Center (CNRC); YUAN, ZHEN - Huazhong University Of Science And Technology; SHEN, YAFENG - Shanghai Jiaotong University; YANG, CHAOFENG - University Of Texas Southwestern Medical Center; ZHAO, JINGXUAN - Tongji Medical College; SHAO, MENGLE - Chinese Academy Of Sciences; CHEN, SHE - National Institute Of Biological Science; BICKEL, PERRY - University Of Texas Southwestern Medical Center; ZHONG, QING - Shanghai Jiaotong University

Submitted to: Cell Discovery
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/8/2023
Publication Date: 11/21/2023
Citation: Fu, Y., Ding, B., Liu, X., Zhao, S., Chen, F., Li, L., Zhu, Y., Yuan, Z., Shen, Y., Yang, C., Zhao, J., Shao, M., Chen, S., Bickel, P.E., Zhong, Q. 2023. Qa-SNARE syntaxin 18 mediates lipid droplet fusion with SNAP23 and SEC22B. Cell Discovery. 9. Article 115. https://doi.org/10.1038/s41421-023-00613-4.
DOI: https://doi.org/10.1038/s41421-023-00613-4

Interpretive Summary: Lipid droplets (LDs) are storage organelles that can respond to changes in energy balance. The size and number of LDs are controlled by complex mechanisms, including the SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptors) proteins that mediate LD fusion, though the details of this process are not well understood. The study identified a specific SNARE complex, involving the proteins syntaxin 18, SNAP23, and SEC22B, that drives LD fusion, and showed that this process is promoted by the protein CIDEC/FSP27.

Technical Abstract: 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 (soluble N-ethylmaleimide sensitive factor attachment protein receptors)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.