mTOR controls neurotoxic lysosome exocytosis in inflammatory reactive astrocytes


Journal article


B. Rooney, K. Leng, F. McCarthy, ***IVL. Rose, KA. Herrington, S. Bax, MY. Chin, S. Fathi, M. Leonetti, A. Kao, J. Elias, M. Kampmann
2021

Semantic Scholar DOI
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APA   Click to copy
Rooney, B., Leng, K., McCarthy, F., Rose, ***I. V. L., Herrington, K. A., Bax, S., … Kampmann, M. (2021). mTOR controls neurotoxic lysosome exocytosis in inflammatory reactive astrocytes.


Chicago/Turabian   Click to copy
Rooney, B., K. Leng, F. McCarthy, ***IVL. Rose, KA. Herrington, S. Bax, MY. Chin, et al. “MTOR Controls Neurotoxic Lysosome Exocytosis in Inflammatory Reactive Astrocytes” (2021).


MLA   Click to copy
Rooney, B., et al. MTOR Controls Neurotoxic Lysosome Exocytosis in Inflammatory Reactive Astrocytes. 2021.


BibTeX   Click to copy

@article{b2021a,
  title = {mTOR controls neurotoxic lysosome exocytosis in inflammatory reactive astrocytes},
  year = {2021},
  author = {Rooney, B. and Leng, K. and McCarthy, F. and Rose, ***IVL. and Herrington, KA. and Bax, S. and Chin, MY. and Fathi, S. and Leonetti, M. and Kao, A. and Elias, J. and Kampmann, M.}
}

Abstract

Inflammatory reactive astrocytes lose homeostatic functions and can be neurotoxic, potentially contributing to neurodegenerative diseases. However, the underlying cell biological mechanisms are not fully understood. Here, we demonstrate that lysosomes are remodeled and alkalinized in inflammatory reactive astrocytes, and that lysosome exocytosis drives astrocyte-mediated neurotoxicity. CRISPRi screens uncover mTOR as a regulator of neurotoxic lysosome exocytosis. These results pinpoint lysosome remodeling and exocytosis in inflammatory reactive astrocytes as a potential therapeutic target.


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