Galectin-9 binding to cell surface protein disulfide isomerase regulates the redox environment to enhance T-cell migration and HIV entry

• DOI: 10.1073/pnas.1017954108
• Publication Date: 2011-06-14T18:03:48Z
• Authors: Shuguang Bi; Patrick W. Hong; Benhur Lee; Linda G. Baum
• Keywords: Electrophoresis; CD4-Positive T-Lymphocytes; 0301 basic medicine; 1.1 Normal biological development and functioning; Galectins; Blotting, Western; Protein Disulfide-Isomerases; Inbred C57BL; Membrane Fusion; Cell Line; Mice; 03 medical and health sciences; Clinical Research; Underpinning research; Cell Movement; Animals; Humans; Polyacrylamide Gel; Blotting; Cell Membrane; 3. Good health; Mice, Inbred C57BL; Infectious Diseases; HIV-1; HIV/AIDS; Electrophoresis, Polyacrylamide Gel; Generic health relevance; Infection; Western; Oxidation-Reduction; Protein Binding

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.