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The B cell‐specific major raft protein, Raftlin, is necessary for the integrity of lipid raft and BCR signal transduction
Author(s) -
Saeki Kazuko,
Miura Yoshiki,
Aki Daisuke,
Kurosaki Tomohiro,
Yoshimura Akihiko
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg293
Subject(s) - biology , raft , signal transduction , microbiology and biotechnology , lipid raft , signal transducing adaptor protein , breakpoint cluster region , genetics , receptor , chemistry , organic chemistry , copolymer , polymer
Recent evidence indicates that membrane microdomains, termed lipid rafts, have a role in B‐cell activation as platforms for B‐cell antigen receptor (BCR) signal initiation. To gain an insight into the possible functioning of lipid rafts in B cells, we applied liquid chromatography electrospray ionization tandem mass spectrometry (LC‐ESI‐MS/MS) methodologies to the identification of proteins that co‐purified with lipid rafts of Raji cells. Among these raft proteins, we characterized a novel protein termed Raftlin ( raft ‐ lin king protein). Like the Src family kinase, Raftlin is localized exclusively in lipid rafts by fatty acylation of N‐terminal Gly2 and Cys3, and is co‐localized with BCR before and after BCR stimulation. Disruption of the Raftlin gene in the DT40 B‐cell line resulted in a marked reduction in the quantity of lipid raft components, including Lyn and ganglioside GM1, while overexpression of Raftlin increased the content of raft protein. Moreover, BCR‐mediated tyrosine phosphorylation and calcium mobilization were impaired by the lack of Raftlin and actually potentiated by overexpression of Raftlin. These data suggest that Raftlin plays a pivotal role in the formation and/or maintenance of lipid rafts, therefore regulating BCR‐mediated signaling.