title: Cutting edge: negative regulation of immune synapse formation by anchoring lipid raft to cytoskeleton through Cbp-EBP50-ERM assembly.
abstract: Ag recognition by T lymphocytes induces immune synapse formation and recruitment of signaling molecules into a lipid raft. Cbp/PAG is a Csk-associated membrane adapter protein exclusively localized in a lipid raft. We identified NHERF/EBP50 as a Cbp-binding molecule, which connects the membrane raft and cytoskeleton by binding to both Cbp through its PDZ domain and ezrin-radixin-moesin through the C terminus. Overexpression of Cbp reduced the mobility of the raft on the cell surface of unstimulated T cells and prevented synapse formation and subsequent T cell activation, whereas a mutant incapable of EBP50 binding restored both synapse formation and activation. These results suggest that anchoring of lipid raft to the cytoskeleton through Cbp-EBP50-ezrin-radixin-moesin assembly regulates membrane dynamism for synapse formation and T cell activation.
authors.affiliation: Department of Molecular Genetics and General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Itoh
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sakakibara
authors.forename: Sho
authors.initials: S
authors.lastname: Yamasaki
authors.forename: Arata
authors.initials: A
authors.lastname: Takeuchi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Arase
authors.forename: Masaru
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Nakajima
authors.forename: Masato
authors.initials: M
authors.lastname: Okada
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002450:Cell Communication / Q000276:immunology; D003599:Cytoskeleton / Q000276:immunology / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation / Q000276:immunology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D021962:Membrane Microdomains / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction / Q000276:immunology; D017923:Sodium-Hydrogen Exchangers; D013601:T-Lymphocytes / Q000276:immunology; D014157:Transcription Factors / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C086680:ETV5 protein, human; C513242:Etv5 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C498710:PAG1 protein, human; C408344:Pag protein, mouse; C498709:Pag1 protein, mouse; D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; D014157:Transcription Factors; C093376:sodium-hydrogen exchanger regulatory factor