The orphan adapter protein SLY1 as a novel anti-apoptotic protein required for thymocyte development

BMC Immunol. 2009 Jul 15:10:38. doi: 10.1186/1471-2172-10-38.

Abstract

Background: SH3 containing Lymphocyte Protein (SLY1) is a putative adapter protein exclusively expressed in lymphocytes which is involved in antigen receptor induced activation. We previously have generated SLY1Delta/Delta mice harbouring a partial deletion in the N-terminal region of SLY1 which revealed profound immunological defects in T and B cell functions.

Results: In this study, T cell development in SLY1-/- and SLY1Delta/Delta mice was analysed ex vivo and upon cultivation with the bone marrow stromal cell line OP9. SLY1-deficient thymocytes were compromised in inducing nutrient receptor expression and ribosomal protein S6 phosphorylation, indicating a defect in mTOR complex activation. Furthermore, SLY1 was identified as a novel anti-apoptotic protein required for developmental progression of T cell precursors to the CD4+CD8+ double-positive stage by protecting from premature programmed cell death initiation in developing CD4-CD8- double-negative thymocytes. In addition, SLY1 phosphorylation was differentially regulated upon Notch ligand-mediated stimulation and expression of the preTCR.

Conclusion: Thus, our results suggest a non-redundant role for SLY1 in integrating signals from both receptors in early T cell progenitors in the thymus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / immunology
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adaptor Proteins, Vesicular Transport
  • Animals
  • Apoptosis
  • CD4 Antigens
  • CD8 Antigens
  • Cell Differentiation
  • Cell Line
  • Gene Expression Regulation, Developmental
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / immunology
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Lymphocyte Activation
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Precursor Cells, T-Lymphoid / cytology
  • Precursor Cells, T-Lymphoid / immunology
  • Precursor Cells, T-Lymphoid / metabolism*
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism*
  • Receptors, Notch / immunology
  • Receptors, Notch / metabolism
  • Signal Transduction / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / growth & development
  • Thymus Gland / immunology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • CD4 Antigens
  • CD8 Antigens
  • Inhibitor of Apoptosis Proteins
  • Membrane Glycoproteins
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Notch
  • SLY1 protein, mouse
  • pre-T cell receptor alpha