@article{oai:tohoku-mpu.repo.nii.ac.jp:00000768,
 author = {永福, 正和 and Nagafuku, Masakazu and 豊島, かおる and Toshima, Kaoru and 堀内, 隼 and Horiuchi, Jun and 井ノ口, 仁一 and Inokuchi, Jin-ichi},
 issue = {65},
 journal = {東北医科薬科大学研究誌, Journal of Tohoku Medical and Pharmaceutical University},
 month = {Dec},
 note = {sphingolipids, including sphingomyelin（sM）and glycosphingolipids（gsLs）, associate with cholesterol to form membrane lipid microdomains in which specific receptors and signaling molecules are localized or recruited to mediate intracellular signaling. During T-cell activation, T cell antigen receptor（Tcr）signaling clusters are formed in membrane lipid microdomains. in this study, we investigated the role of individual lipid microdomains constructed from sM and gsLs on Tcr signaling. SM synthase 1（sMs1）is primarily responsible for SM synthesis; glucosylceramide synthase（glccers）is the enzyme responsible for the synthesis of glccer, which is the precursor for more complex gsLs such as gangliosides. We established sMs1 mutant and glccers mutant Jurkat cells using the crisPr/cas9 system. in sMs1 mutant cells, sM-microdomain levels on the cell surface were nearly deficient, although cellular sM levels decreased by half compared with Jurkat cells. glccers mutant cells did not express any kind of GSLs, while Jurkat cells expressed GlcCer and a-series gangliosides（such as GM3, GM2, GM1 and GD1a）. We then examined the phosphorylation of ZAP-70（a TCR-proximal kinase）, intracellular calcium mobilization, and the expression of CD69（an early activation marker of T cells）by TCR stimulation in the mutant cells; all these TCR-induced signaling events were greatly enhanced in SMS1 mutant cells, but not in GlcCers mutant cells. The enhanced response to TCR stimulation in SMS1 mutant cells were restored by reintroduction of SMS1 gene. These findings indicate that SM-microdomains acts negative regulators of TCR signal transduction.},
 pages = {29--42},
 title = {スフィンゴミエリンマイクロドメインはJurkat細胞のT細胞抗原受容体依存性の活性化を負に制御する},
 year = {2018},
 yomi = {ナガフク, マサカズ and トシマ, カオル and ホリウチ, ジュン and イノクチ, ジンイチ}
}