title: Galectin-9 binding to cell surface protein disulfide isomerase regulates the redox environment to enhance T-cell migration and HIV entry.
abstract: Interaction of cell surface glycoproteins with endogenous lectins on the cell surface regulates formation and maintenance of plasma membrane domains, clusters signaling complexes, and controls the residency time of glycoproteins on the plasma membrane. Galectin-9 is a soluble, secreted lectin that binds to glycoprotein receptors to form galectin-glycoprotein lattices on the cell surface. Whereas galectin-9 binding to specific glycoprotein receptors induces death of CD4 Th1 cells, CD4 Th2 cells are resistant to galectin-9 death due to alternative glycosylation. On Th2 cells, galectin-9 binds cell surface protein disulfide isomerase (PDI), increasing retention of PDI on the cell surface and altering the redox status at the plasma membrane. Cell surface PDI regulates integrin function on platelets and also enhances susceptibility of T cells to infection with HIV. We find that galectin-9 binding to PDI on Th2 cells results in increased cell migration through extracellular matrix via β3 integrins, identifying a unique mechanism to regulate T-cell migration. In addition, galectin-9 binding to PDI on T cells potentiates infection with HIV. We identify a mechanism for regulating cell surface redox status via a galectin-glycoprotein lattice, to regulate distinct T-cell functions.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California School of Medicine, Los Angeles, CA 90095, USA.
authors.forename: Shuguang
authors.initials: S
authors.lastname: Bi
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Hong
authors.forename: Benhur
authors.initials: B
authors.lastname: Lee
authors.forename: Linda G
authors.initials: LG
authors.lastname: Baum
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D004591:Electrophoresis, Polyacrylamide Gel; D037161:Galectins / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008561:Membrane Fusion; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D011485:Protein Binding; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*
chemical_list: D037161:Galectins; C105032:LGALS9 protein, human; D019704:Protein Disulfide-Isomerases