Atg1 kinase regulates autophagosome-vacuole fusion by controlling SNARE bundling.
Atg1 kinase regulates autophagosome-vacuole fusion by controlling SNARE bundling.
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DOI：
10.15252/embr.202051869
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发表时间：
2020-12-03
期刊：
影响因子：
7.7
通讯作者：
Kraft C
中科院分区：
文献类型：
--
作者：
Barz S;Kriegenburg F;Henning A;Bhattacharya A;Mancilla H;Sánchez-Martín P;Kraft C
自噬介导细胞质物质的降解。自噬诱导后，自噬体在货物周围形成密封膜，并与裂解隔室融合以释放货物进行降解。为了避免不成熟的自噬体膜与裂解隔室过早融合，需要严格调节该过程。最近已经确定了几种介导自噬体-空泡融合的因子。在芽殖酵母中，自噬体-空泡融合需要自噬体上的R-SNARE Ykt 6，以及空泡上的三个Q-SNARE Vam 3，Vam 7和Vti 1。然而，这些SNARE在融合过程中是如何调节的，人们还知之甚少。在这项研究中，我们研究了Ykt 6的调控。我们发现Ykt 6被Atg 1激酶直接磷酸化，这使这个SNARE处于非活性状态。Ykt 6磷酸化通过破坏其与空泡SNARE Vam 3和Vti 1的相互作用来防止SNARE捆绑，从而防止过早的自噬体-空泡融合。这些发现为自噬体-空泡融合的调节提供了新的线索，并揭示了由Atg 1激酶控制的自噬的进一步步骤。Atg 1激酶通过控制SNARE捆绑和自噬体-空泡融合来调节自噬的晚期步骤。
Autophagy mediates the degradation of cytoplasmic material. Upon autophagy induction, autophagosomes form a sealed membrane around the cargo and fuse with the lytic compartment to release the cargo for degradation. In order to avoid premature fusion of immature autophagosomal membranes with the lytic compartment, this process needs to be tightly regulated. Several factors mediating autophagosome–vacuole fusion have recently been identified. In budding yeast, autophagosome–vacuole fusion requires the R‐SNARE Ykt6 on the autophagosome, together with the three Q‐SNAREs Vam3, Vam7, and Vti1 on the vacuole. However, how these SNAREs are regulated during the fusion process is poorly understood. In this study, we investigate the regulation of Ykt6. We found that Ykt6 is directly phosphorylated by Atg1 kinase, which keeps this SNARE in an inactive state. Ykt6 phosphorylation prevents SNARE bundling by disrupting its interaction with the vacuolar SNAREs Vam3 and Vti1, thereby preventing premature autophagosome–vacuole fusion. These findings shed new light on the regulation of autophagosome–vacuole fusion and reveal a further step in autophagy controlled by the Atg1 kinase. Atg1 kinase regulates late steps in autophagy by controlling SNARE bundling and autophagosome‐vacuole fusion.