Cutting edge: negative regulation of immune synapse formation by anchoring lipid raft to cytoskeleton through Cbp-EBP50-ERM assembly

Katsuhiko Itoh; Masahiro Sakakibara; Sho Yamasaki; Arata Takeuchi; Hisashi Arase; Masaru Miyazaki; Nobuyuki Nakajima; Masato Okada; Takashi Saito

doi:10.4049/jimmunol.168.2.541

Cutting edge: negative regulation of immune synapse formation by anchoring lipid raft to cytoskeleton through Cbp-EBP50-ERM assembly

J Immunol. 2002 Jan 15;168(2):541-4. doi: 10.4049/jimmunol.168.2.541.

Authors

Katsuhiko Itoh¹, Masahiro Sakakibara, Sho Yamasaki, Arata Takeuchi, Hisashi Arase, Masaru Miyazaki, Nobuyuki Nakajima, Masato Okada, Takashi Saito

Affiliation

¹ Department of Molecular Genetics and General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.

PMID: 11777944
DOI: 10.4049/jimmunol.168.2.541

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing
Animals
Carrier Proteins / metabolism*
Cell Communication / immunology
Cytoskeleton / immunology
Cytoskeleton / metabolism*
DNA-Binding Proteins / metabolism*
Down-Regulation / immunology*
Humans
Intercellular Signaling Peptides and Proteins
Jurkat Cells
Lymphocyte Activation
Membrane Microdomains / immunology
Membrane Microdomains / metabolism*
Membrane Proteins / genetics
Membrane Proteins / metabolism*
Mice
Mice, Inbred BALB C
Phosphoproteins / genetics
Phosphoproteins / metabolism*
Phosphorylation
Signal Transduction / immunology
Sodium-Hydrogen Exchangers*
T-Lymphocytes / immunology
Transcription Factors / metabolism*
Two-Hybrid System Techniques

Substances

Adaptor Proteins, Signal Transducing
Carrier Proteins
DNA-Binding Proteins
ETV5 protein, human
Etv5 protein, mouse
Intercellular Signaling Peptides and Proteins
Membrane Proteins
PAG1 protein, human
Pag protein, mouse
Pag1 protein, mouse
Phosphoproteins
Sodium-Hydrogen Exchangers
Transcription Factors
sodium-hydrogen exchanger regulatory factor