自噬体的静电成熟

Autophagy Pub Date : 2024-10-01 Epub Date: 2024-07-06 DOI:10.1080/15548627.2024.2375082
Saori Shinoda, Noboru Mizushima
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引用次数: 0

摘要

在大自噬过程中,溶酶体会与封闭的自噬体融合,但不会与未封闭的自噬体融合。这至少部分是通过自噬体 SNARE STX17(句法酶 17)与成熟自噬体的时间调控招募来实现的。然而,STX17 识别自噬体成熟的分子机制仍然未知。我们最近的研究发现,STX17 的招募受 STX17 带正电荷的 C 端区域与自噬体膜之间静电相互作用的调控,而自噬体膜在成熟过程中由于磷脂酰肌醇-4-磷酸(PtdIns4P)的积累而变成带负电荷。在这里,我们提出了自噬体的静电成熟模型。
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Electrostatic maturation of the autophagosome.

In macroautophagy, lysosomes fuse with closed autophagosomes but not with unclosed ones. This is achieved, at least in part, by the temporally regulated recruitment of the autophagosomal SNARE STX17 (syntaxin 17) to only mature autophagosomes. However, the molecular mechanism by which STX17 recognizes autophagosomal maturation remains unknown. Our recent study revealed that STX17 recruitment is regulated by the electrostatic interaction between the positively charged C-terminal region of STX17 and the autophagosomal membrane, which becomes negatively charged during maturation due to the accumulation of phosphatidylinositol-4-phosphate (PtdIns4P). Here, we propose an electrostatic maturation model of the autophagosome.

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