Cutting edge: negative regulation of immune synapse formation by anchoring lipid raft to cytoskeleton through Cbp-EBP50-ERM assembly.
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.
Itoh
Katsuhiko
K
Department of Molecular Genetics and General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Sakakibara
Masahiro
M
Yamasaki
Sho
S
Takeuchi
Arata
A
Arase
Hisashi
H
Miyazaki
Masaru
M
Nakajima
Nobuyuki
N
Okada
Masato
M
Saito
Takashi
T
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
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