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mTOR controls lysosome tubulation and antigen presentation in macrophages and dendritic cells

Macrophages and dendritic cells exposed to lipopolysaccharide (LPS) convert their lysosomes from small, punctate organelles into a network of tubules. Tubular lysosomes have been implicated in phagosome maturation, retention of fluid phase, and antigen presentation. There is a growing appreciation t...

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Autores principales: Saric, Amra, Hipolito, Victoria E. B., Kay, Jason G., Canton, Johnathan, Antonescu, Costin N., Botelho, Roberto J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4713134/
https://www.ncbi.nlm.nih.gov/pubmed/26582390
http://dx.doi.org/10.1091/mbc.E15-05-0272
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author Saric, Amra
Hipolito, Victoria E. B.
Kay, Jason G.
Canton, Johnathan
Antonescu, Costin N.
Botelho, Roberto J.
author_facet Saric, Amra
Hipolito, Victoria E. B.
Kay, Jason G.
Canton, Johnathan
Antonescu, Costin N.
Botelho, Roberto J.
author_sort Saric, Amra
collection PubMed
description Macrophages and dendritic cells exposed to lipopolysaccharide (LPS) convert their lysosomes from small, punctate organelles into a network of tubules. Tubular lysosomes have been implicated in phagosome maturation, retention of fluid phase, and antigen presentation. There is a growing appreciation that lysosomes act as sensors of stress and the metabolic state of the cell through the kinase mTOR. Here we show that LPS stimulates mTOR and that mTOR is required for LPS-induced lysosome tubulation and secretion of major histocompatibility complex II in macrophages and dendritic cells. Specifically, we show that the canonical phosphatidylinositol 3-kinase–Akt–mTOR signaling pathway regulates LPS-induced lysosome tubulation independently of IRAK1/4 and TBK. Of note, we find that LPS treatment augmented the levels of membrane-associated Arl8b, a lysosomal GTPase required for tubulation that promotes kinesin-dependent lysosome movement to the cell periphery, in an mTOR-dependent manner. This suggests that mTOR may interface with the Arl8b-kinesin machinery. To further support this notion, we show that mTOR antagonists can block outward movement of lysosomes in cells treated with acetate but have no effect in retrograde movement upon acetate removal. Overall our work provides tantalizing evidence that mTOR plays a role in controlling lysosome morphology and trafficking by modulating microtubule-based motor activity in leukocytes.
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spelling pubmed-47131342016-03-30 mTOR controls lysosome tubulation and antigen presentation in macrophages and dendritic cells Saric, Amra Hipolito, Victoria E. B. Kay, Jason G. Canton, Johnathan Antonescu, Costin N. Botelho, Roberto J. Mol Biol Cell Articles Macrophages and dendritic cells exposed to lipopolysaccharide (LPS) convert their lysosomes from small, punctate organelles into a network of tubules. Tubular lysosomes have been implicated in phagosome maturation, retention of fluid phase, and antigen presentation. There is a growing appreciation that lysosomes act as sensors of stress and the metabolic state of the cell through the kinase mTOR. Here we show that LPS stimulates mTOR and that mTOR is required for LPS-induced lysosome tubulation and secretion of major histocompatibility complex II in macrophages and dendritic cells. Specifically, we show that the canonical phosphatidylinositol 3-kinase–Akt–mTOR signaling pathway regulates LPS-induced lysosome tubulation independently of IRAK1/4 and TBK. Of note, we find that LPS treatment augmented the levels of membrane-associated Arl8b, a lysosomal GTPase required for tubulation that promotes kinesin-dependent lysosome movement to the cell periphery, in an mTOR-dependent manner. This suggests that mTOR may interface with the Arl8b-kinesin machinery. To further support this notion, we show that mTOR antagonists can block outward movement of lysosomes in cells treated with acetate but have no effect in retrograde movement upon acetate removal. Overall our work provides tantalizing evidence that mTOR plays a role in controlling lysosome morphology and trafficking by modulating microtubule-based motor activity in leukocytes. The American Society for Cell Biology 2016-01-15 /pmc/articles/PMC4713134/ /pubmed/26582390 http://dx.doi.org/10.1091/mbc.E15-05-0272 Text en © 2016 Saric et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Saric, Amra
Hipolito, Victoria E. B.
Kay, Jason G.
Canton, Johnathan
Antonescu, Costin N.
Botelho, Roberto J.
mTOR controls lysosome tubulation and antigen presentation in macrophages and dendritic cells
title mTOR controls lysosome tubulation and antigen presentation in macrophages and dendritic cells
title_full mTOR controls lysosome tubulation and antigen presentation in macrophages and dendritic cells
title_fullStr mTOR controls lysosome tubulation and antigen presentation in macrophages and dendritic cells
title_full_unstemmed mTOR controls lysosome tubulation and antigen presentation in macrophages and dendritic cells
title_short mTOR controls lysosome tubulation and antigen presentation in macrophages and dendritic cells
title_sort mtor controls lysosome tubulation and antigen presentation in macrophages and dendritic cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4713134/
https://www.ncbi.nlm.nih.gov/pubmed/26582390
http://dx.doi.org/10.1091/mbc.E15-05-0272
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