Erythroid Differentiation Regulator 1 Strengthens TCR Signaling by Enhancing PLCγ1 Signal Transduction Pathway

Int J Mol Sci. 2022 Jan 13;23(2):844. doi: 10.3390/ijms23020844.

Abstract

Erythroid differentiation regulator 1 (Erdr1) has previously been reported to control thymocyte selection via TCR signal regulation, but the effect of Erdr1 as a TCR signaling modulator was not studied in peripheral T cells. In this report, it was determined whether Erdr1 affected TCR signaling strength in CD4 T cells. Results revealed that Erdr1 significantly enhanced the anti-TCR antibody-mediated activation and proliferation of T cells while failing to activate T cells in the absence of TCR stimulation. In addition, Erdr1 amplified Ca2+ influx and the phosphorylation of PLCγ1 in CD4 T cells with the TCR stimuli. Furthermore, NFAT1 translocation into nuclei in CD4 T cells was also significantly promoted by Erdr1 in the presence of TCR stimulation. Taken together, our results indicate that Erdr1 positively modulates TCR signaling strength via enhancing the PLCγ1/Ca2+/NFAT1 signal transduction pathway.

Keywords: Erdr1; PLCγ1; TCR signal modulation.

MeSH terms

  • Animals
  • Biomarkers
  • Calcium / metabolism
  • Calcium Signaling
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Immunophenotyping
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Mice
  • Phospholipase C gamma / metabolism
  • Phosphorylation
  • Receptors, Antigen, T-Cell / metabolism
  • Signal Transduction*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Biomarkers
  • Membrane Proteins
  • Receptors, Antigen, T-Cell
  • Tumor Suppressor Proteins
  • erythroid differentiation regulator 1, mouse
  • Phospholipase C gamma
  • Plcg1 protein, mouse
  • Calcium

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