title: LFA-1-dependent lipid raft recruitment of DNAM-1 (CD226) in CD4+ T cell.
abstract: Upon antigen recognition by the TCR, both the leukocyte adhesion molecules DNAM-1 and leukocyte function-associated antigen-1 (LFA-1) associate with lipid rafts and form peripheral supra-molecular activation clusters that surround central-supra-molecular activation clusters at the immunological synapse. The serine residue in the cytoplasmic tail of DNAM-1 is responsible for this association of DNAM-1 with lipid rafts. The TCR-mediated signal also induces physical association of DNAM-1 with LFA-1, for which the serine phosphorylation of DNAM-1 is also responsible. However, how the serine residue is involved in lipid raft recruitment of DNAM-1 has remained unclear. Here, we show that, although the TCR-mediated signal induced the serine phosphorylation of DNAM-1, DNAM-1 did not associate with lipid rafts in CD4+ T cells derived from mice deficient in LFA-1 expression, indicating that lipid raft recruitment of DNAM-1 depends on LFA-1 expression. These results suggest that the serine phosphorylation of DNAM-1 primarily induces physical association of DNAM-1 with LFA-1, which then takes DNAM-1 into lipid raft compartment.
authors.affiliation: Department of Immunology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences and Center for TARA, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Shirakawa
authors.forename: Yinan
authors.initials: Y
authors.lastname: Wang
authors.forename: Satoko
authors.initials: S
authors.lastname: Tahara-Hanaoka
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Honda
authors.forename: Kazuko
authors.initials: K
authors.lastname: Shibuya
authors.forename: Akira
authors.initials: A
authors.lastname: Shibuya
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015870:Gene Expression / Q000235:genetics / Q000276:immunology; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000276:immunology*; D021962:Membrane Microdomains / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011499:Protein Processing, Post-Translational / Q000276:immunology*; D017434:Protein Structure, Tertiary / Q000235:genetics; D021381:Protein Transport / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell