Control of vacuole membrane homeostasis by a resident PI-3,5-kinase inhibitor.
Control of vacuole membrane homeostasis by a resident PI-3,5-kinase inhibitor.
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DOI：
10.1073/pnas.1722517115
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发表时间：
2018-05-01
影响因子：
11.1
通讯作者：
Ungermann C
中科院分区：
文献类型：
--
作者：
Malia PC;Numrich J;Nishimura T;González Montoro A;Stefan CJ;Ungermann C
溶酶体样液泡是降解膜蛋白和细胞器的主要细胞器，因此为细胞存活提供氨基酸和离子。因此，维持液泡膜的完整性对细胞适应是重要的。液泡表面含有多种蛋白质复合物以维持液泡的功能，其中一种复合物是名为Fab1的脂质激酶（在人类细胞中属于PIKfyve）。Fab1是产生磷酸化脂质pi -3,5- p2的蛋白质复合体的一部分。其他蛋白质结合pi -3,5- p2，并可以在压力下使液泡破碎以平衡体积和膜。我们现在确定Ivy1是一种结合Fab1并控制其活性的蛋白质。溶酶体在细胞蛋白和细胞器质量控制、代谢和信号传导中具有重要作用。在溶酶体表面，PIKfyve/Fab1复合体生成磷脂酰肌醇3,5-二磷酸，pi -3,5- p2，这对于急性渗透胁迫下溶酶体膜稳态和溶酶体信号传导至关重要。在这里，我们确定了倒置BAR蛋白Ivy1作为Fab1复合物的抑制剂，直接影响pi -3,5- p2水平和液泡稳态。Ivy1需要与Ypt7结合才能发挥作用，与pi -3,5- p2结合，并与Fab1激酶相互作用。在渗透胁迫下，Ivy1和Fab1的共定位丢失。与Ivy1作为Fab1调节因子的作用一致，它的过表达在渗透休克和液泡破裂过程中阻断Fab1的活性。相反，Ivy1的缺失或Ivy1在液泡上远离Fab1的侧向重新定位，会导致液泡破碎和生长不良。我们的数据表明，Ivy1在膜胁迫过程中调节fab1介导的pi -3,5- p2合成，并可能调节液泡膜环境。
The lysosome-like vacuole is the main organelle to degrade membrane proteins and organelles and, thus, provides amino acids, but also ions to the cytosol for cellular survival. Maintenance of vacuole membrane integrity is thus important for cellular adaptations. The vacuole contains several protein complexes on its surface to maintain the vacuole functional, and one such complex is a lipid kinase named Fab1 (of PIKfyve in human cells). Fab1 is part of a protein complex that produces a phosphorylated lipid, PI-3,5-P2. Other proteins bind PI-3,5-P2 and can fragment the vacuole to balance volume vs. membrane during stress. We now identify Ivy1 as a protein that binds Fab1 and controls its activity. Lysosomes have an important role in cellular protein and organelle quality control, metabolism, and signaling. On the surface of lysosomes, the PIKfyve/Fab1 complex generates phosphatidylinositol 3,5-bisphosphate, PI-3,5-P2, which is critical for lysosomal membrane homeostasis during acute osmotic stress and for lysosomal signaling. Here, we identify the inverted BAR protein Ivy1 as an inhibitor of the Fab1 complex with a direct influence on PI-3,5-P2 levels and vacuole homeostasis. Ivy1 requires Ypt7 binding for its function, binds PI-3,5-P2, and interacts with the Fab1 kinase. Colocalization of Ivy1 and Fab1 is lost during osmotic stress. In agreement with Ivy1’s role as a Fab1 regulator, its overexpression blocks Fab1 activity during osmotic shock and vacuole fragmentation. Conversely, loss of Ivy1, or lateral relocalization of Ivy1 on vacuoles away from Fab1, results in vacuole fragmentation and poor growth. Our data suggest that Ivy1 modulates Fab1-mediated PI-3,5-P2 synthesis during membrane stress and may allow adjustment of the vacuole membrane environment.
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影响因子：
3.3
作者：
Lürick A;Gao J;Kuhlee A;Yavavli E;Langemeyer L;Perz A;Raunser S;Ungermann C
通讯作者：
Ungermann C
影响因子：
16.6
作者：
Dong, Xian-ping;Shen, Dongbiao;Wang, Xiang;Dawson, Taylor;Li, Xinran;Zhang, Qi;Cheng, Xiping;Zhang, Yanling;Weisman, Lois S.;Delling, Markus;Xu, Haoxing
通讯作者：
Xu, Haoxing
DOI：
10.1083/jcb.201304123
发表时间：
2013-10-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Araki Y;Ku WC;Akioka M;May AI;Hayashi Y;Arisaka F;Ishihama Y;Ohsumi Y
通讯作者：
Ohsumi Y
DOI：
10.1083/jcb.143.1.65
发表时间：
1998-10-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gary JD;Wurmser AE;Bonangelino CJ;Weisman LS;Emr SD
通讯作者：
Emr SD
影响因子：
3.3
作者：
Li, Sheena Claire;Diakov, Theodore T.;Kane, Patricia M.
通讯作者：
Kane, Patricia M.