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

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Serval ID
serval:BIB_A3A49137D91C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Functional glycosylation of dystroglycan is crucial for thymocyte development in the mouse.
Journal
Plos One
Author(s)
Liou Li-Ying, Walsh Kevin B., Vartanian Arineh R., de Bernabe Daniel Beltran-Valero, Welch Megan, Campbell  Kevin P., Oldstone Michael B. A., Kunz Stefan
ISSN
1932-6203[electronic], 1932-6203[linking]
Publication state
Published
Issued date
2010
Volume
5
Number
3
Pages
9915
Language
english
Notes
Publication Status: epublish
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.
Keywords
T-Cell Development, Alpha-Dystroglycan, Immunological Synapse, Viral-Infection, Survival, Thymus, CD8(+), Virus, Organization, Lymphocytes
Pubmed
Web of science
Open Access
Yes
Create date
20/04/2010 15:54
Last modification date
20/08/2019 15:09
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