Post-translational control of T cell development by the ESCRT protein CHMP5 Academic Article uri icon

Overview

MeSH Major

  • Cell Differentiation
  • Endosomal Sorting Complexes Required for Transport
  • Receptors, Antigen, T-Cell
  • T-Lymphocytes
  • Thymocytes

abstract

  • The acquisition of a protective vertebrate immune system hinges on the efficient generation of a diverse but self-tolerant repertoire of T cells by the thymus through mechanisms that remain incompletely resolved. Here we identified the endosomal-sorting-complex-required-for-transport (ESCRT) protein CHMP5, known to be required for the formation of multivesicular bodies, as a key sensor of thresholds for signaling via the T cell antigen receptor (TCR) that was essential for T cell development. CHMP5 enabled positive selection by promoting post-selection thymocyte survival in part through stabilization of the pro-survival protein Bcl-2. Accordingly, loss of CHMP5 in thymocyte precursor cells abolished T cell development, a phenotype that was 'rescued' by genetic deletion of the pro-apoptotic protein Bim or transgenic expression of Bcl-2. Mechanistically, positive selection resulted in the stabilization of CHMP5 by inducing its interaction with the deubiquitinase USP8. Our results thus identify CHMP5 as an essential component of the post-translational machinery required for T cell development.

publication date

  • June 20, 2017

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1038/ni.3764

PubMed ID

  • 28553951

Additional Document Info

start page

  • 780

end page

  • 790

volume

  • 18

number

  • 7