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A selective PIKfyve inhibitor blocks PtdIns(3,5)P 2 production and disrupts endomembrane transport and retroviral budding
Open accessAbstract
Phosphoinositides have crucial roles in cellular controls, many of which have been established through the use of small‐molecule inhibitors. Here, we describe YM201636, a potent inhibitor of the mammalian class III phosphatidylinositol phosphate kinase PIKfyve, which synthesizes phosphatidylinositol 3,5‐bisphosphate. Acute treatment of cells with YM201636 shows that the PIKfyve pathway is involved in the sorting of endosomal transport, with inhibition leading to the accumulation of a late endosomal compartment and blockade of retroviral exit. Inhibitor specificity is shown by the use of short interfering RNA against the target, as well as by rescue with the drug‐resistant yeast orthologue Fab1. We concluded that the phosphatidylinositol 3,5‐bisphosphate pathway is integral to endosome formation, determining morphology and cargo flux.
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Cites
LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y., & Yoshimori, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5720 · Cited by 6,605
Fab1p PtdIns(3)P 5-Kinase Function Essential for Protein Sorting in the Multivesicular Body
Odorizzi, G., Babst, M., & Emr, S. D. (1998) · Cell · doi:10.1016/s0092-8674(00)81707-9 · Cited by 656
Gaullier, J.-M., Simonsen, A., D'Arrigo, A., Bremnes, B., Stenmark, H., & Aasland, R. (1998) · Nature · doi:10.1038/28767 · Cited by 553
Role of ESCRT-I in Retroviral Budding
Martin-Serrano, J., Zang, T., & Bieniasz, P. D. (2003) · Journal of Virology · doi:10.1128/jvi.77.8.4794-4804.2003 · Cited by 250
Cited by
Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation
Balla, T. (2013) · Physiological Reviews · doi:10.1152/physrev.00028.2012 · Cited by 1,638
A molecular mechanism to regulate lysosome motility for lysosome positioning and tubulation
Li, X., Rydzewski, N., Hider, A., Zhang, X., Yang, J., Wang, W., Gao, Q., Cheng, X., & Xu, H. (2016) · Nature Cell Biology · doi:10.1038/ncb3324 · Cited by 387
A TRP Channel in the Lysosome Regulates Large Particle Phagocytosis via Focal Exocytosis
Samie, M., Wang, X., Zhang, X., Goschka, A., Li, X., Cheng, X., Gregg, E., Azar, M., Zhuo, Y., Garrity, A. G., et al. (2013) · Developmental Cell · doi:10.1016/j.devcel.2013.08.003 · Cited by 317
PIKfyve inhibition increases exosome release and induces secretory autophagy
Hessvik, N. P., Øverbye, A., Brech, A., Torgersen, M. L., Jakobsen, I. S., Sandvig, K., & Llorente, A. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2309-8 · Cited by 269
Zolov, S. N., Bridges, D., Zhang, Y., Lee, W.-W., Riehle, E., Verma, R., Lenk, G. M., Converso-Baran, K., Weide, T., Albin, R. L., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1203106109 · Cited by 236
Metadata
- Authors
- Jefferies, H. B. J., Cooke, F. T., Jat, P., Boucheron, C., Koizumi, T., Hayakawa, M., Kaizawa, H., Ohishi, T., Workman, P., Waterfield, M. D., & Parker, P. J.
- Venue
- EMBO reports
- Published
- 2008-01-11
- Volume
- 9
- Issue
- 2
- Pages
- 164-170
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- OpenAlex
- W2118278336
- Cited by
- 301
- References
- 4
- FWCI
- 4.86
- Type
- journal article
- Language
- en
- Open access
- green
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- Jefferies, H. B. J., Cooke, F. T., Jat, P., Boucheron, C., Koizumi, T., Hayakawa, M., Kaizawa, H., Ohishi, T., Workman, P., Waterfield, M. D., & Parker, P. J. (2008). A selective PIKfyve inhibitor blocks PtdIns(3,5)P 2 production and disrupts endomembrane transport and retroviral budding. EMBO reports. https://doi.org/10.1038/sj.embor.7401155
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
