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| Status |
Public on Jan 07, 2020 |
| Title |
Enhanced and selective translation expands the lysosome size and promotes antigen presentation during phagocyte activation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The mechanisms that govern organelle remodeling remain poorly defined. Lysosomes degrade cargo from various routes including endocytosis, phagocytosis and autophagy. For phagocytes, lysosomes are a kingpin organelle since they are essential to kill pathogens and process and present antigens. During phagocyte activation, lysosomes undergo a striking reorganization, changing from dozens of globular structures to a tubular network, in a process that requires the phosphatidylinositol-3-kinase-AKT-mTOR signalling pathway. Here, we show that lysosomes undergo a remarkable expansion in volume and holding capacity during phagocyte activation within 2 h of LPS stimulation. Lysosome expansion was paralleled by an increase in lysosomal protein levels, but this was unexpectedly independent of TFEB and TFE3 transcription factors, known to scale up lysosome biogenesis. Instead, we demonstrate a hitherto unappreciated mechanism of acute organelle expansion via mTORC1-dependent increase in translation of mRNAs encoding key lysosomal proteins. Importantly, mTORC1-dependent increase in translation activity was necessary for efficient and rapid antigen presentation by dendritic cells. Collectively, we identified a previously unknown and functionally relevant mechanism for lysosome expansion that relies on mTORC1-dependent enhanced translation of mRNAs to boost protein synthesis and lysosome biogenesis in response to an infection signal.
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| Overall design |
Polysome profiling of RAW cells treated with 2h or 6h LPS, LPS in the presence of Torin1, Torin1 or DMSO.
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| Contributor(s) |
Hipolito VE, Diaz JA, Tandoc KV, Oertlin C, Ristau J, Chauhan N, Saric A, Mclaughlan S, Larsson O, Topisirovic I, Botelho RJ |
| Citation(s) |
31800587 |
| Submission date |
Aug 27, 2019 |
| Last update date |
Jan 08, 2020 |
| Contact name |
Christian Oertlin |
| E-mail(s) |
christian.oertlin@ki.se
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| Organization name |
Karolinska Institutet
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| Street address |
Tomtebodavägen 23A
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| City |
Stockholm |
| ZIP/Postal code |
17165 |
| Country |
Sweden |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA562562 |
| SRA |
SRP219915 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE136470_rawcounts.txt.gz |
447.3 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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