文章基本信息

标题：Control of vacuole membrane homeostasis by a resident PI-3,5-kinase inhibitor
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作者：PC Malia ; Johannes Numrich ; Taki Nishimura 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2018
卷号：115
期号：18
页码：4684-4689
DOI：10.1073/pnas.1722517115
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
关键词：Ivy1 ; Fab1 ; IBAR ; lysosome ; osmotic stress