mTOR controls lysosome tubulation and antigen presentation in macrophages and dendritic cells
Autor: | Jason G. Kay, Roberto J. Botelho, Johnathan Canton, Costin N. Antonescu, Victoria E. B. Hipolito, Amra Saric |
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Rok vydání: | 2023 |
Předmět: |
0301 basic medicine
Endosome Antigen presentation Endosomes Major histocompatibility complex Mice Phosphatidylinositol 3-Kinases 03 medical and health sciences 0302 clinical medicine Lysosome Phagosome maturation medicine Animals Secretion Molecular Biology PI3K/AKT/mTOR pathway Antigen Presentation biology ADP-Ribosylation Factors Macrophages TOR Serine-Threonine Kinases Articles Dendritic Cells Cell Biology 3. Good health Cell biology Mice Inbred C57BL Oncogene Protein v-akt Toll-Like Receptor 4 Protein Transport RAW 264.7 Cells 030104 developmental biology medicine.anatomical_structure Membrane Trafficking biology.protein Female Signal transduction Lysosomes 030217 neurology & neurosurgery Signal Transduction |
Zdroj: | Molecular Biology of the Cell |
Popis: | LPS causes lysosome tubulation in macrophages and dendritic cells. The PI3K-Akt-mTOR pathway is necessary for LPS-induced lysosome tubulation, and mTOR is required for MHC-II presentation in dendritic cells. Evidence shows that mTOR may control lysosome tubulation by modulating microtubule motor activity through Arl8b. 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. |
Databáze: | OpenAIRE |
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