Contribution of T Cell Receptor Signaling Pathways to Ribosomal Biosynthesis 2260618

Abstract

Abstract Introduction In the early phase of T cell activation the cells increase in size about five times before they divide about three times per day. These processes require the rapid upregulation of macromolecular biosynthesis. We have asked how TCR signaling pathways upregulate ribosomal biosynthesis. Methods We visualized ribosomal biosynthesis by cytometric quantification: The cellular RNA content was detected by dye stainings, rRNA precursors by FISH probes and translational activity by puromycilation. Results We have seen previously that T cells lacking mTORC1 express just half the amount of ribosomes and translational capacity. Cells lacking the mTORC1 targets S6 kinases 1 and 2 display a high sensitivity to Raf, MEK and Rsk inhibition, indicating a partial compensation by the MAP kinase pathway. Cells deleted of the Malt1 or Bcl10 components of the CBM complex or an inhibited Malt1 paracaspase activity display a reduction of rRNA synthesis of about one third, while cells with an inhibited Conclusion These data show that the MAP kinase and NF-kB signaling pathways contribute to the upregulation of ribosomal biosynthesis in activated T cells and thus to their increased biomass production. Funding Source German Research Council Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)