Functional glycosylation of dystroglycan is crucial for thymocyte development in the mouse

PLoS One. 2010 Mar 29;5(3):e9915. doi: 10.1371/journal.pone.0009915.

Abstract

Background: Alpha-dystroglycan (alpha-DG) is a cell surface receptor providing a molecular link between the extracellular matrix (ECM) and the actin-based cytoskeleton. During its biosynthesis, alpha-DG undergoes specific and unusual O-glycosylation crucial for its function as a high-affinity cellular receptor for ECM proteins.

Methodology/principal findings: We report that expression of functionally glycosylated alpha-DG during thymic development is tightly regulated in developing T cells and largely confined to CD4(-)CD8(-) double negative (DN) thymocytes. Ablation of DG in T cells had no effect on proliferation, migration or effector function but did reduce the size of the thymus due to a significant loss in absolute numbers of thymocytes. While numbers of DN thymocytes appeared normal, a marked reduction in CD4(+)CD8(+) double positive (DP) thymocytes occurred. In the periphery mature naïve T cells deficient in DG showed both normal proliferation in response to allogeneic cells and normal migration, effector and memory T cell function when tested in acute infection of mice with either lymphocytic choriomeningitis virus (LCMV) or influenza virus.

Conclusions/significance: Our study demonstrates that DG function is modulated by glycosylation during T cell development in vivo and that DG is essential for normal development and differentiation of T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / chemistry
  • Animals
  • Cell Cycle
  • Cell Membrane / metabolism
  • Cytoskeleton / metabolism
  • Dystroglycans / chemistry*
  • Dystroglycans / metabolism*
  • Extracellular Matrix / metabolism
  • Flow Cytometry / methods
  • Glycosylation*
  • Humans
  • Lymphocytic choriomeningitis virus / metabolism
  • Mice
  • Orthomyxoviridae / metabolism
  • T-Lymphocytes / cytology
  • Thymus Gland / cytology*

Substances

  • Actins
  • Dystroglycans