Functional Glycosylation of Dystroglycan Is Crucial for Thymocyte Development in the Mouse

Li-Ying Liou; Kevin B Walsh; Arineh R Vartanian; Daniel Beltran-Valero de Bernabe; Megan Welch; Kevin P Campbell; Michael B. A Oldstone; Stefan Kunz

doi:10.1371/journal.pone.0009915

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Functional Glycosylation of Dystroglycan Is Crucial for Thymocyte Development in the Mouse

Journal article

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Functional Glycosylation of Dystroglycan Is Crucial for Thymocyte Development in the Mouse

Li-Ying Liou, Kevin B Walsh, Arineh R Vartanian, Daniel Beltran-Valero de Bernabe, Megan Welch, Kevin P Campbell, Michael B. A Oldstone and Stefan Kunz

PloS one, Vol.5(3), pp.e9915-e9915

2010

DOI: 10.1371/journal.pone.0009915

PMCID: PMC2848029

PMID: 20369005

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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.

Immunology

Developmental Biology

Cell Biology

Extra-Cellular Matrix

Leukocyte Development

Details

Title: Subtitle: Functional Glycosylation of Dystroglycan Is Crucial for Thymocyte Development in the Mouse
Creators: Li-Ying Liou
Kevin B Walsh
Arineh R Vartanian
Daniel Beltran-Valero de Bernabe
Megan Welch
Kevin P Campbell
Michael B. A Oldstone
Stefan Kunz
Resource Type: Journal article
Publication Details: PloS one, Vol.5(3), pp.e9915-e9915
DOI: 10.1371/journal.pone.0009915
PMID: 20369005
PMCID: PMC2848029
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; San Francisco, USA
Alternative title: Dystroglycan in T Cells
Language: English
Date published: 2010
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
Record Identifier: 9984020855502771

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