論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pQE30/His6-Venus-NT-Lys (RDB13959) pQE30/His6-mRFP-NT-Lys (RDB13960) |