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.

Peri/Epicellular Protein Disulfide Isomerase Sustains Vascular Lumen Caliber Through an Anticonstrictive Remodeling Effect

“…29 Our data add to other specific effects of pecPDI pool, which include immune reactions, 16 pathogen response, 16,27 and thrombosis. [18][19][20][21] Subcellular routes of PDI externalization remain elusive.…”

“…Vascular hydrogen peroxide production was assessed using Amplex Red assay. 16 Cell-surface biotinylation of extracellular-free thiols was performed after labeling with 200 μmol/L 3-(N-maleimidopropionyl) biocytin.…”

“…To address vascular pecPDI effects, we performed loss-offunction experiments using well-validated [16][17][18][19] neutralizing antibodies: either the RL90 (Thermo-Pierce) or 34(BD) clones. Because intracellular PDI supports protein folding and protects against ER stress, we addressed whether pecPDI affects ER stress.…”

“…As periand epicellular PDI are often indistinguishable, we coined the term peri/epicellular (pec) PDI to designate the extracellular pool. PecPDI mediates many thiol redox-dependent processes, including virus internalization, 16 galectin binding, 16 metalloproteinase regulation, 17 integrin signaling, and platelet aggregation. 18 Importantly, pecPDI sustains injury-associated thrombosis, 19 and inhibitors of PDI family proteins are among the most innovative antithrombotic strategies.…”

Identification of inhibition of protein disulphide isomerase expression related to classical swine fever virus infection by using real-time PCR analysis

“…[12,13] In addition, PDI plays an important role in the host cell invasion process by HIV-1 and the dengue virus. [14,15] For example, during the entry of HIV-1 into the host cells, the fusion of HIV-1 capsule membrane and the cell membrane depends on the PDI functional sites. [16] During the virusÀcell interaction period, PDI inhibitors could prevent decomposition of disulphide bonds and prevent the entry of HIV-1.…”