VAMP8 phosphorylation regulates lysosome dynamics during autophagy.
VAMP8 phosphorylation regulates lysosome dynamics during autophagy.
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DOI：
10.1080/27694127.2022.2031378
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发表时间：
2022
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在自噬降解的最后一个关键步骤中，溶酶体与自噬体融合形成自噬体。虽然最近的研究表明可溶性n -乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）蛋白对溶酶体与自噬体融合很重要，但预融合状态的结构和调节机制都没有被确定。在我们的研究中，使用结构照明显微镜，我们观察到溶酶体在单个自噬体周围形成簇，从而为膜融合奠定了基础。此外，VAMP8（囊泡相关膜蛋白8）有助于形成这些团簇的预融合状态。我们还发现，VAMP8磷酸化减少了自发溶酶体与自噬体的融合，而在正常和自噬诱导条件下，它的去磷酸化促进了溶酶体与自噬体之间的融合事件。因此，我们的数据表明VAMP8磷酸化在溶酶体-自噬体融合的调节中起关键作用。
In the final critical step for autophagic degradation, lysosomes fuse with autophagosomes to form autolysosomes. Although recent research has suggested that soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins are important for lysosome-autophagosome fusion, neither the architecture of the prefusion state nor the regulatory mechanisms have been identified. In our study, using structured illumination microscopy, we observed that lysosomes formed clusters around individual autophagosomes, thereby setting the stage for membrane fusion. Moreover, VAMP8 (vesicle-associated membrane protein 8) assists in forming the prefusion state of these clusters. We also found that VAMP8 phosphorylation reduces spontaneous lysosome-autophagosome fusion, whereas its dephosphorylation promotes fusion events between lysosomes and autophagosomes in both normal and autophagy-induced conditions. Our data thus suggest a key role of VAMP8 phosphorylation in the regulation of lysosome-autophagosome fusion.