Neomycin toxicity in eukaryotic cells stems from its binding to phosphoinositides, primarily confined to the inner leaflet of the plasma membrane. New research reveals a complex lipid-trafficking pathway that exposes phosphatidylinositol 4-phosphate on the cell surface and identifies Neo1 as a flippase that limits this exposure.
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References
Masur, H., Whelton, P. K. & Whelton, A. Arch. Surg. 111, 822–825 (1976).
Au, S., Weiner, N. D. & Schacht, J. Biochim. Biophys. Acta 902, 80–86 (1987).
Carney, D. H., Scott, D. L., Gordon, E. A. & LaBelle, E. F. Cell 42, 479–488 (1985).
Kobayashi, T. & Menon, A. K. Curr. Biol. 28, R386–R391 (2018).
Jain, B. et al. Nat. Cell Biol. https://doi.org/10.1038/s41556-025-01692-z (2025).
Sakuragi, T. & Nagata, S. Nat. Rev. Mol. Cell Biol. 24, 576–596 (2023).
Prezant, T. R., Chaltraw, W. E. Jr & Fischel-Ghodsian, N. Microbiology 142, 3407–3414 (1996).
Wong, A. K. O., Young, B. P. & Loewen, C. J. R. J. Cell Biol. 220, e201910161 (2021).
Sebinelli, H.G. et al. Preprint at bioRxiv https://doi.org/10.1101/2025.02.13.638165 (2025).
Yoneda, A. et al. Biochem. Biophys. Res. Commun. 527, 1050–1056 (2020).
Gulshan, K. et al. Circ. Res. 119, 827–838 (2016).
Wang, H. et al. Mol. Cell 73, 458–473.E7 (2019).
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Salsaa, M., Fairn, G.D. Phosphoinositide flipping governs neomycin sensitivity. Nat Cell Biol 27, 1057–1058 (2025). https://doi.org/10.1038/s41556-025-01707-9
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DOI: https://doi.org/10.1038/s41556-025-01707-9