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Function of the SNARE Ykt6 on autophagosomes requires the Dsl1 complex and the Atg1 kinase complex
EMBO Reports ( IF 6.5 ) Pub Date : 2020-10-07 , DOI: 10.15252/embr.202050733
Jieqiong Gao 1 , Rainer Kurre 2, 3 , Jaqueline Rose 1 , Stefan Walter 2 , Florian Fröhlich 4 , Jacob Piehler 2, 3, 5 , Fulvio Reggiori 6 , Christian Ungermann 1, 2
Affiliation  

The mechanism and regulation of fusion between autophagosomes and lysosomes/vacuoles are still only partially understood in both yeast and mammals. In yeast, this fusion step requires SNARE proteins, the homotypic vacuole fusion and protein sorting (HOPS) tethering complex, the RAB7 GTPase Ypt7, and its guanine nucleotide exchange factor (GEF) Mon1‐Ccz1. We and others recently identified Ykt6 as the autophagosomal SNARE protein. However, it has not been resolved when and how lipid‐anchored Ykt6 is recruited onto autophagosomes. Here, we show that Ykt6 is recruited at an early stage of the formation of these carriers through a mechanism that depends on endoplasmic reticulum (ER)‐resident Dsl1 complex and COPII‐coated vesicles. Importantly, Ykt6 activity on autophagosomes is regulated by the Atg1 kinase complex, which inhibits Ykt6 through direct phosphorylation. Thus, our findings indicate that the Ykt6 pool on autophagosomal membranes is kept inactive by Atg1 phosphorylation, and once an autophagosome is ready to fuse with vacuole, Ykt6 dephosphorylation allows its engagement in the fusion event.

中文翻译:

自噬体上 SNARE Ykt6 的功能需要 Dsl1 复合物和 Atg1 激酶复合物

在酵母和哺乳动物中,自噬体和溶酶体/液泡之间融合的机制和调控仍只是部分了解。在酵母中,此融合步骤需要 SNARE 蛋白、同型液泡融合和蛋白质分选 (HOPS) 束缚复合物、RAB7 GTPase Ypt7 及其鸟嘌呤核苷酸交换因子 (GEF) Mon1-Ccz1。我们和其他人最近将 Ykt6 鉴定为自噬体 SNARE 蛋白。然而,脂质锚定的 Ykt6 何时以及如何被募集到自噬体上尚未得到解决。在这里,我们表明 Ykt6 在这些载体形成的早期阶段通过依赖于内质网 (ER) 驻留的 Dsl1 复合物和 COPII 包被的囊泡的机制被招募。重要的是,Ykt6 对自噬体的活性受 Atg1 激酶复合物的调节,通过直接磷酸化抑制 Ykt6。因此,我们的研究结果表明,自噬体膜上的 Ykt6 池通过 Atg1 磷酸化保持不活跃,一旦自噬体准备好与液泡融合,Ykt6 去磷酸化使其参与融合事件。
更新日期:2020-12-10
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