title: Trafficking of LAG-3 to the surface on activated T cells via its cytoplasmic domain and protein kinase C signaling.
abstract: Lymphocyte activation gene-3 (LAG-3; CD223), a structural homolog of CD4, binds to MHC class II molecules. Recent research indicated that signaling mediated by LAG-3 inhibits T cell proliferation, and LAG-3 serves as a key surface molecule for the function of regulatory T cells. Previous reports demonstrated that the majority of LAG-3 is retained in the intracellular compartments and is rapidly translocated to the cell surface upon stimulation. However, the mechanism by which LAG-3 translocates to the cell surface was unclear. In this study, we examined the trafficking of human LAG-3 under unstimulated as well as stimulated conditions of T cells. Under the unstimulated condition, the majority of LAG-3 did not reach the cell surface, but rather degraded within the lysosomal compartments. After stimulation, the majority of LAG-3 translocated to the cell surface without degradation in the lysosomal compartments. Results indicated that the cytoplasmic domain without Glu-Pro repetitive sequence is critical for the translocation of LAG-3 from lysosomal compartments to the cell surface. Moreover, protein kinase C signaling leads to the translocation of LAG-3 to the cell surface. However, two potential serine phosphorylation sites from the LAG-3 cytoplasmic domain are not involved in the translocation of LAG-3. These results clearly indicate that LAG-3 trafficking from lysosomal compartments to the cell surface is dependent on the cytoplasmic domain through protein kinase C signaling in activated T cells.
authors.affiliation: Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 136-701, Republic of Korea;
authors.forename: Joonbeom
authors.initials: J
authors.lastname: Bae
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Cheongju University, Cheongju-si, 360-764, Republic of Korea; and.
authors.forename: Suk Jun
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea.
authors.forename: Chung-Gyu
authors.initials: CG
authors.lastname: Park
authors.affiliation: Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 136-701, Republic of Korea;
authors.forename: Young Sik
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 136-701, Republic of Korea; tchun@korea.ac.kr.
authors.forename: Taehoon
authors.initials: T
authors.lastname: Chun
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015704:CD4 Antigens / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004151:Dipeptides / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology*; D008247:Lysosomes; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D008565:Membrane Proteins; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D015398:Signal Transduction / Q000276:immunology; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; D015704:CD4 Antigens; D004151:Dipeptides; D061965:Matrix Metalloproteinase Inhibitors; D008565:Membrane Proteins; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D011493:Protein Kinase C; D000093322:Lymphocyte Activation Gene 3 Protein; C000720326:Lag3 protein, human