TCR and IL-7 Signaling Are Altered in the Absence of Functional GTPase of the Immune Associated Nucleotide Binding Protein 5 (GIMAP5)

PLoS One. 2016 Mar 29;11(3):e0151837. doi: 10.1371/journal.pone.0151837. eCollection 2016.

Abstract

GTPase of the immune associated nucleotide binding protein (GIMAP) family of proteins are expressed essentially in cells of the hematopoietic system. Mutation in the founding member of this gene family, Gimap5, results in the lymphopenic phenotype in Bio-Breeding diabetes prone rats. In mice, deletion of functional Gimap5 gene affects the survival and renewal of hematopoietic stem cells in addition to the defects observed in T cells. Here we show that T cells from OTII TCR-transgenic Gimap5sph/sph mice do not proliferate in response to its cognate antigen. Furthermore, T cells from Gimap5 mutant rats and mice show decreased phosphorylation of STAT5 following stimulation with IL-7. Our results suggest that functional Gimap5 is required for optimal signaling through TCR and IL-7R in T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD3 Complex / metabolism
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Down-Regulation
  • GTP Phosphohydrolases / deficiency
  • GTP Phosphohydrolases / metabolism*
  • GTP-Binding Proteins / deficiency
  • GTP-Binding Proteins / metabolism*
  • Interleukin-7 / metabolism*
  • Mice, Transgenic
  • Microtubules / metabolism
  • Phosphorylation
  • Protein Transport
  • Rats
  • Receptors, Antigen, T-Cell / metabolism*
  • STAT5 Transcription Factor / metabolism
  • Signal Transduction*

Substances

  • CD3 Complex
  • Gimap5 protein, mouse
  • Interleukin-7
  • Receptors, Antigen, T-Cell
  • STAT5 Transcription Factor
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • Gimap5 protein, rat