CCL5-mediated T-cell chemotaxis involves the initiation of mRNA translation through mTOR/4E-BPl

Thomas T. Murooka, Ramtin Rahbar, Leonidas C. Platanias, Eleanor N. Fish

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

The multistep, coordinated process of T-cell chemotaxis requires chemokines, and their chemokine receptors, to invoke signaling events to direct cell migration. Here, we examined the role for CCL5- mediated initiation of mRNA translation in CD4 + T-cell chemotaxis. Using rapamycin, an inhibitor of mTOR, our data show the importance of mTOR in CCL5-mediated T-cell migration. Cycloheximide, but not actinomycin D, significantly reduced chemotaxis, suggesting a possible role for mRNA translation in T-cell migration. CCL5 induced phosphorylation/activation of mTOR, p70 S6K1, and ribosomal protein S6. In addition, CCL5 induced PI-3'K-, phospholipase D (PLD)-, and mTOR-dependent phosphorylation and deactivation of the transcriptional repressor 4E-BP1, which resulted in its dissociation from the eukaryotic initiation factor-4E (elF4E). Subsequently, elF4E associated with scaffold protein elF4G, forming the elF4F translation initiation complex. Indeed, CCL5 initiated active translation of mRNA, shown by the increased presence of high-molecular-weight polysomes that were significantly reduced by rapamycin treatment. Notably, CCL5 induced protein translation of cyclin D1 and MMP-9, known mediators of migration. Taken together, we describe a novel mechanism by which CCL5 influences translation of rapamycin-sensitive mRNAs and "primes" CD4 + T cells for efficient chemotaxis.

Original languageEnglish (US)
Pages (from-to)4892-4901
Number of pages10
JournalBlood
Volume111
Issue number10
DOIs
StatePublished - May 15 2008

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'CCL5-mediated T-cell chemotaxis involves the initiation of mRNA translation through mTOR/4E-BPl'. Together they form a unique fingerprint.

Cite this