突触表蛋白-1通过相分离来调节其钙敏感性寡聚。

IF 7.4 1区 生物学 Q1 CELL BIOLOGY Journal of Cell Biology Pub Date : 2024-10-07 Epub Date: 2024-07-09 DOI:10.1083/jcb.202311191
Min Zhu, Han Xu, Yulei Jin, Xiaoxu Kong, Bingkuan Xu, Yinghui Liu, Haijia Yu
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引用次数: 0

摘要

突触标签蛋白-1(Syt1)是一种钙传感器,在神经递质同步释放过程中调节突触囊泡的融合。Syt1 与带负电荷的脂质和 SNARE 复合物相互作用,控制融合过程。然而,人们对 Syt1 如何介导 Ca2+ 触发的突触囊泡融合仍不甚了解。在这里,我们发现 Syt1 在体外和活细胞中都会发生液-液相分离(LLPS),形成凝聚物。Syt1凝聚物在囊泡附着到PM上发挥作用,并能有效招募SNAREs和复合素,这可能会促进下游突触囊泡的融合。我们观察到,Syt1凝聚物经历了从液态到凝胶状的相变,这反映了Syt1低聚物的形成。这种相变可被 Ca2+ 阻断或逆转,证实了 Ca2+ 在 Syt1 寡聚体解体过程中的重要作用。最后,我们发现,导致Syt1相关神经发育障碍的Syt1突变会损害Ca2+驱动的相变。这些发现揭示了Syt1经历了LLPS和Ca2+敏感的相变,为Syt1介导的囊泡融合提供了新的见解。
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Synaptotagmin-1 undergoes phase separation to regulate its calcium-sensitive oligomerization.

Synaptotagmin-1 (Syt1) is a calcium sensor that regulates synaptic vesicle fusion in synchronous neurotransmitter release. Syt1 interacts with negatively charged lipids and the SNARE complex to control the fusion event. However, it remains incompletely understood how Syt1 mediates Ca2+-trigged synaptic vesicle fusion. Here, we discovered that Syt1 undergoes liquid-liquid phase separation (LLPS) to form condensates both in vitro and in living cells. Syt1 condensates play a role in vesicle attachment to the PM and efficiently recruit SNAREs and complexin, which may facilitate the downstream synaptic vesicle fusion. We observed that Syt1 condensates undergo a liquid-to-gel-like phase transition, reflecting the formation of Syt1 oligomers. The phase transition can be blocked or reversed by Ca2+, confirming the essential role of Ca2+ in Syt1 oligomer disassembly. Finally, we showed that the Syt1 mutations causing Syt1-associated neurodevelopmental disorder impair the Ca2+-driven phase transition. These findings reveal that Syt1 undergoes LLPS and a Ca2+-sensitive phase transition, providing new insights into Syt1-mediated vesicle fusion.

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来源期刊
Journal of Cell Biology
Journal of Cell Biology 生物-细胞生物学
CiteScore
12.60
自引率
2.60%
发文量
213
审稿时长
1 months
期刊介绍: The Journal of Cell Biology (JCB) is a comprehensive journal dedicated to publishing original discoveries across all realms of cell biology. We invite papers presenting novel cellular or molecular advancements in various domains of basic cell biology, along with applied cell biology research in diverse systems such as immunology, neurobiology, metabolism, virology, developmental biology, and plant biology. We enthusiastically welcome submissions showcasing significant findings of interest to cell biologists, irrespective of the experimental approach.
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