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Control of vacuole membrane homeostasis by a resident PI-3,5-kinase inhibitor
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-P(2), which is critical for lysosomal membrane homeostasis during acute osmotic...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5939101/ https://www.ncbi.nlm.nih.gov/pubmed/29674454 http://dx.doi.org/10.1073/pnas.1722517115 |
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author | Malia, PC Numrich, Johannes Nishimura, Taki González Montoro, Ayelén Stefan, Christopher J. Ungermann, Christian |
author_facet | Malia, PC Numrich, Johannes Nishimura, Taki González Montoro, Ayelén Stefan, Christopher J. Ungermann, Christian |
author_sort | Malia, PC |
collection | PubMed |
description | 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-P(2), 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-P(2) levels and vacuole homeostasis. Ivy1 requires Ypt7 binding for its function, binds PI-3,5-P(2), 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-P(2) synthesis during membrane stress and may allow adjustment of the vacuole membrane environment. |
format | Online Article Text |
id | pubmed-5939101 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-59391012018-05-09 Control of vacuole membrane homeostasis by a resident PI-3,5-kinase inhibitor Malia, PC Numrich, Johannes Nishimura, Taki González Montoro, Ayelén Stefan, Christopher J. Ungermann, Christian Proc Natl Acad Sci U S A Biological Sciences 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-P(2), 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-P(2) levels and vacuole homeostasis. Ivy1 requires Ypt7 binding for its function, binds PI-3,5-P(2), 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-P(2) synthesis during membrane stress and may allow adjustment of the vacuole membrane environment. National Academy of Sciences 2018-05-01 2018-04-19 /pmc/articles/PMC5939101/ /pubmed/29674454 http://dx.doi.org/10.1073/pnas.1722517115 Text en Copyright © 2018 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Malia, PC Numrich, Johannes Nishimura, Taki González Montoro, Ayelén Stefan, Christopher J. Ungermann, Christian Control of vacuole membrane homeostasis by a resident PI-3,5-kinase inhibitor |
title | Control of vacuole membrane homeostasis by a resident PI-3,5-kinase inhibitor |
title_full | Control of vacuole membrane homeostasis by a resident PI-3,5-kinase inhibitor |
title_fullStr | Control of vacuole membrane homeostasis by a resident PI-3,5-kinase inhibitor |
title_full_unstemmed | Control of vacuole membrane homeostasis by a resident PI-3,5-kinase inhibitor |
title_short | Control of vacuole membrane homeostasis by a resident PI-3,5-kinase inhibitor |
title_sort | control of vacuole membrane homeostasis by a resident pi-3,5-kinase inhibitor |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5939101/ https://www.ncbi.nlm.nih.gov/pubmed/29674454 http://dx.doi.org/10.1073/pnas.1722517115 |
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