Open AccessCutting Edge: Negative Regulation of Immune Synapse Formation by Anchoring Lipid Raft to Cytoskeleton Through Cbp-EBP50-ERM Assembly
Author(s) -
Katsuhiko Itoh,
Masahiro Sakakibara,
Sho Yamasaki,
Arata Takeuchi,
Hisashi Arase,
Masaru Miyazaki,
Nobuyuki Nakajima,
Masato Okada,
Takashi Saito
Publication year - 2002
Publication title -
the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.168.2.541
Subject(s) - immunological synapse , microbiology and biotechnology , lipid raft , radixin , ezrin , pdz domain , moesin , cytoskeleton , jurkat cells , signal transducing adaptor protein , raft , biology , chemistry , signal transduction , t cell , cell , t cell receptor , biochemistry , immune system , immunology , organic chemistry , copolymer , polymer
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.
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