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


RESULTS
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
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.
Liou
Li-Ying
LY
Viral-Immunobiology Laboratory, Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America.
Walsh
Kevin B
KB
Vartanian
Arineh R
AR
Beltran-Valero de Bernabe
Daniel
D
Welch
Megan
M
Campbell
Kevin P
KP
Oldstone
Michael B A
MB
Kunz
Stefan
S
D000199:Actins / Q000737:chemistry; D000818:Animals; D002453:Cell Cycle; D002462:Cell Membrane / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D049030:Dystroglycans / Q000737:chemistry* / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D006031:Glycosylation; D006801:Humans; D008217:Lymphocytic choriomeningitis virus / Q000378:metabolism; D051379:Mice; D009975:Orthomyxoviridae / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology*
D000199:Actins; D049030:Dystroglycans