A sorting nexin PpAtg24 regulates vacuolar membrane dynamics during pexophagy via binding to phosphatidylinositol-3-phosphate
A sorting nexin PpAtg24 regulates vacuolar membrane dynamics during pexophagy via binding to phosphatidylinositol-3-phosphate
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DOI：
10.1091/mbc.e04-09-0842
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发表时间：
2005-02-01
影响因子：
3.3
通讯作者：
Sakai, Y
中科院分区：
文献类型：
--
作者：
Ano, Y;Hattori, T;Sakai, Y
不同的细胞过程，如自噬蛋白的降解，需要真核细胞中的肌醇磷脂信号。在巴斯德毕赤酵母中，过氧化物体可以通过两种吞噬途径选择性地降解，即大噬噬和微噬。两者都涉及液泡表面的膜融合事件，其特征是融合复合体的边界区域内部化，表明融合发生在顶端。在这里，我们证明了PpAtg24，一个具有磷脂酰肌醇3-磷酸结合模块(Px结构域)的分子，是吞噬作用所必需的，在液泡表面的膜融合中发挥功能。CFP标记的PpAtg24定位于噬菌体-空泡融合复合体的顶端和边界区。PpAtg24缺失导致噬菌体形成后和融合前大噬菌体被阻断。这些和其他结果表明，PpAtg24通过与磷脂酰肌醇3-磷酸结合参与了吞噬过程中液泡表面膜融合的时空调节，而不是先前提出的在吞噬液泡形成过程中的作用。
Diverse cellular processes such as autophagic protein degradation require phosphoinositide signaling in eukaryotic cells. In the methylotrophic yeast Pichia pastoris, peroxisomes can be selectively degraded via two types of pexophagic pathways, macropexophagy and micropexophagy. Both involve membrane fusion events at the vacuolar surface that are characterized by internalization of the boundary domain of the fusion complex, indicating that fusion occurs at the vertex. Here, we show that PpAtg24, a molecule with a phosphatidylinositol 3-phosphate-binding module (PX domain) that is indispensable for pexophagy, functions in membrane fusion at the vacuolar surface. CFP-tagged PpAtg24 localized to the vertex and boundary region of the pexophagosome-vacuole fusion complex during macropexophagy. Depletion of PpAtg24 resulted in the blockage of macropexophagy after pexophagosome formation and before the fusion stage. These and other results suggest that PpAtg24 is involved in the spatiotemporal regulation of membrane fusion at the vacuolar surface during pexophagy via binding to phosphatidylinositol 3-phosphate, rather than the previously suggested function in formation of the pexophagosome.