| RRC ID |
36036
|
| 著者 |
Kiyokawa E, Baba T, Otsuka N, Makino A, Ohno S, Kobayashi T.
|
| タイトル |
Spatial and functional heterogeneity of sphingolipid-rich membrane domains.
|
| ジャーナル |
J Biol Chem
|
| Abstract |
Little is known about the organization of lipids in biomembranes. Lipid rafts are defined as sphingolipid- and cholesterol-rich clusters in the membrane. Details of the lipid distribution of lipid rafts are not well characterized mainly because of a lack of appropriate probes. Ganglioside GM1-specific protein, cholera toxin, has long been the only lipid probe of lipid rafts. Recently it was shown that earthworm toxin, lysenin, specifically recognizes sphingomyelin-rich membrane domains. Binding of lysenin to sphingomyelin is accompanied by the oligomerization of the toxin that leads to pore formation in the target membrane. In this study, we generated a truncated lysenin mutant that does not oligomerize and thus is non-toxic. Using this mutant lysenin, we showed that plasma membrane sphingomyelin-rich domains are spatially distinct from ganglioside GM1-rich membrane domains in Jurkat T cells. Like T cell receptor activation and cross-linking of GM1, cross-linking of sphingomyelin induced calcium influx and ERK phosphorylation in the cell. However, unlike CD3 or GM1, cross-linking of sphingomyelin did not induce significant protein tyrosine phosphorylation. Combination of lysenin and sphingomyelinase treatment suggested the involvement of G-protein-coupled receptor in sphingomyelin-mediated signal transduction. These results thus suggest that the sphingomyelin-rich domain provides a functional signal cascade platform that is distinct from those provided by T cell receptor or GM1. Our study therefore elucidates the spatial and functional heterogeneity of lipid rafts.
|
| 巻・号 |
280(25)
|
| ページ |
24072-84
|
| 公開日 |
2005-6-24
|
| DOI |
10.1074/jbc.M502244200
|
| PII |
S0021-9258(20)67464-6
|
| PMID |
15840575
|
| MeSH |
Cell Line
Flow Cytometry
Fluorescent Antibody Technique
G(M1) Ganglioside / metabolism*
Humans
Mutagenesis
Proteins / genetics
Proteins / metabolism
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Sequence Deletion
Sphingomyelin Phosphodiesterase / genetics
Sphingomyelin Phosphodiesterase / metabolism
Toxins, Biological
|
| IF |
4.238
|
| 引用数 |
125
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| 遺伝子材料 |
pQE30/His6-Venus-NT-Lys (RDB13959)
pQE30/His6-mRFP-NT-Lys (RDB13960) |
