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Reciprocal regulation of mTORC1 and ribosomal biosynthesis determines cell cycle progression in activated T cells
- Source :
- The Journal of Immunology. 206:98.24-98.24
- Publication Year :
- 2021
- Publisher :
- The American Association of Immunologists, 2021.
-
Abstract
- Anabolic metabolism of antigen-stimulated T cells is coordinated by mTOR which is activated by TCR and IL-2 signals. We show that mTORC1 regulates both the exit of quiescence and later divisions as Raptor-deficient T cells proceed 3x slower through each cell division in vivo. We noticed that following stimulation the amount of RNA per cell increases dramatically (10–40x) and is reduced to ~50% in Raptor-, but not Rictor-deficient T cells. RNAseq data indicate that this applies to all RNA polymerase I- and II-dependent biotypes. Using Coulter volume measurements, RNA-, FISH- and imaging-flow cytometry we determined that following stimulation the cell volume increases five-fold. It consists of the increase of nuclear volume and nucleolar rRNA synthesis on day 1 and a further increase of cytoplasmic volume on day 2. Raptor-deficiency delays and diminishes the growth of these cellular compartments, decreases ribosomal biosynthesis and thus the cell volume. Inhibitors of rRNA transcription block cell cycle progression at two checkpoints, of which only the G1/S transition is regulated by Raptor. We found that mTORC1 activity depends on ongoing rRNA synthesis in early activation and regulates the further synthesis rate. Altogether our data show that mTOR-adjusted cell physiology and the biosynthesis of ribosomal ‘hardware’ are reciprocally regulated during clonal T cell expansion.
- Subjects :
- Immunology
Immunology and Allergy
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 206
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi...........7a6e88e1ce1bfea5c6c5d89573cb2ba9