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

Qa-SNARE syntaxin 18 mediates lipid droplet fusion with SNAP23 and SEC22B.
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QA-SNARE Synaxin 18介导脂滴与SNAP23和SEC22B的融合。

DOI:
10.1038/s41421-023-00613-4
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发表时间:
2023-11-21
期刊:
影响因子:
33.5
通讯作者:
Zhong, Qing
Zhong, Qing
中科院分区:
生物学1区
文献类型:
--
作者:
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

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脂滴是一种动态脂质储存细胞器,能够感知和响应全身能量平衡的变化。LD的大小和数量受复杂而微妙的机制控制,其中,SNARE蛋白是否和哪些介导LD融合,以及控制这一过程的机制尚不清楚。在这里,我们发现了一个SNARE复合物syntaxin 18 (STX18) -SNAP23-SEC22B,它被招募到LD中介导LD融合。STX18通过其跨膜结构域两次跨越磷脂单层靶向ld。STX18-SNAP23-SEC22B复合物在脂质体脂质混合和含量混合的体外实验中驱动LD融合。CIDEC/FSP27直接结合STX18、SEC22B和SNAP23,通过促进LD聚类,促进snares重组脂质体的脂质混合。在高脂饮食条件下,通过AAV敲低小鼠肝脏中的STX18,导致肝脏变小,LD减小。所有这些结果都证明了SNARE复合物STX18-SNAP23-SEC22B在LD融合中的关键作用。
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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