Localization of a TORC1-eIF4F translation complex during CD8+ T cell activation drives divergent cell fate

Swantje Liedmann*, Xueyan Liu, Clifford S. Guy, Jeremy Chase Crawford, Diego A. Rodriguez, Duygu Kuzuoğlu-Öztürk, Ao Guo, Katherine C. Verbist, Jamshid Temirov, Mark J. Chen, Davide Ruggero, Hui Zhang, Paul G. Thomas, Douglas R. Green*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Activated CD8+ T lymphocytes differentiate into heterogeneous subsets. Using super-resolution imaging, we found that prior to the first division, dynein-dependent vesicular transport polarized active TORC1 toward the microtubule-organizing center (MTOC) at the proximal pole. This active TORC1 was physically associated with active eIF4F, required for the translation of c-myc mRNA. As a consequence, c-myc-translating polysomes polarized toward the cellular pole proximal to the immune synapse, resulting in localized c-myc translation. Upon division, the TORC1-eIF4A complex preferentially sorted to the proximal daughter cell, facilitating asymmetric c-Myc synthesis. Transient disruption of eIF4A activity at first division skewed long-term cell fate trajectories to memory-like function. Using a genetic barcoding approach, we found that first-division sister cells often displayed differences in transcriptional profiles that largely correlated with c-Myc and TORC1 target genes. Our findings provide mechanistic insights as to how distinct T cell fate trajectories can be established during the first division.

Original languageEnglish (US)
Pages (from-to)2401-2414.e9
JournalMolecular cell
Volume82
Issue number13
DOIs
StatePublished - Jul 7 2022

Keywords

  • CD8 T cells
  • STED
  • STORM
  • asymmetric cell division
  • c-Myc
  • cell fate
  • eIF4A
  • polarization
  • scRNA-seq
  • translation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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