Galectin-9 binds to O-glycans on protein disulfide isomerase

Katrin Schaefer; Nicholas E Webb; Mabel Pang; Jenny E Hernandez-Davies; Katharine P Lee; Pascual Gonzalez; Martin V Douglass; Benhur Lee; Linda G Baum

doi:10.1093/glycob/cwx065

Galectin-9 binds to O-glycans on protein disulfide isomerase

Glycobiology. 2017 Sep 1;27(9):878-887. doi: 10.1093/glycob/cwx065.

Authors

Katrin Schaefer¹, Nicholas E Webb², Mabel Pang¹, Jenny E Hernandez-Davies¹, Katharine P Lee¹, Pascual Gonzalez¹, Martin V Douglass¹, Benhur Lee³, Linda G Baum¹

Affiliations

¹ Department of Pathology and Laboratory Medicine.
² Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
³ Department of Microbiology, Icahn School of Medicine, Mount Sinai, New York, USA.

Abstract

Changes in the T cell surface redox environment regulate critical cell functions, such as cell migration, viral entry and cytokine production. Cell surface protein disulfide isomerase (PDI) contributes to the regulation of T cell surface redox status. Cell surface PDI can be released into the extracellular milieu or can be internalized by T cells. We have found that galectin-9, a soluble lectin expressed by T cells, endothelial cells and dendritic cells, binds to and retains PDI on the cell surface. While endogenous galectin-9 is not required for basal cell surface PDI expression, exogenous galectin-9 mediated retention of cell surface PDI shifted the disulfide/thiol equilibrium on the T cell surface. O-glycans on PDI are required for galectin-9 binding, and PDI recognition appears to be specific for galectin-9, as galectin-1 and galectin-3 do not bind PDI. Galectin-9 is widely expressed by immune and endothelial cells in inflamed tissues, suggesting that T cells would be exposed to abundant galectin-9, in cis and in trans, in infectious or autoimmune conditions.

Keywords: O-glycans; galectin-9; protein disulfide isomerase.

MeSH terms

Binding Sites
Cell Line
Cell Membrane / chemistry
Cell Membrane / drug effects
Cell Membrane / immunology
Cell Membrane / metabolism*
Cloning, Molecular
Escherichia coli / genetics
Escherichia coli / metabolism
Galectin 1 / genetics
Galectin 1 / metabolism*
Galectin 3 / genetics
Galectin 3 / metabolism
Galectins / antagonists & inhibitors
Galectins / genetics
Galectins / metabolism*
Galectins / pharmacology
Gene Expression
Gene Expression Regulation
Glycosylation
Humans
Models, Molecular
Oxidation-Reduction
Polysaccharides / chemistry
Polysaccharides / metabolism
Protein Binding
Protein Disulfide-Isomerases / chemistry
Protein Disulfide-Isomerases / genetics
Protein Disulfide-Isomerases / immunology
Protein Disulfide-Isomerases / metabolism*
Protein Transport
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
Recombinant Fusion Proteins / pharmacology
Signal Transduction
T-Lymphocytes / chemistry
T-Lymphocytes / drug effects
T-Lymphocytes / immunology
T-Lymphocytes / metabolism*

Substances

Galectin 1
Galectin 3
Galectins
LGALS1 protein, human
LGALS9 protein, human
Polysaccharides
RNA, Small Interfering
Recombinant Fusion Proteins
Protein Disulfide-Isomerases

Grants and funding

R21 HL102989/HL/NHLBI NIH HHS/United States