T-Cell Receptor Microclusters Critical for T-Cell Activation Are Formed Independently of Lipid Raft Clustering
T-Cell Receptor Microclusters Critical for T-Cell Activation Are Formed Independently of Lipid Raft Clustering
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DOI：
10.1128/mcb.00160-10
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发表时间：
2010-07-01
影响因子：
5.3
通讯作者：
Saito, Takashi
中科院分区：
文献类型：
--
作者：
Hashimoto-Tane, Akiko;Yokosuka, Tadashi;Saito, Takashi
本文研究了免疫突触上脂筏在T细胞受体微簇（TCR-MCs）和中枢超分子激活簇（cSMACs）的产生和信号传导中的作用。已经表明，脂筏积累在T细胞活化时产生用于募集信号分子的平台。然而，几种脂筏探针没有积累在TCR-MCs或cSMACs，即使与共刺激和TCR或LAT和脂筏探针之间的荧光共振能量转移（FRET）的阳性诱导条件下，在TCR-MCs没有诱导CD 3 zeta和ZAP-70之间的FRET。LAT突变体的分析表明，筏协会是必不可少的膜定位，但TCR-MC的形成。仔细分析筏探针在细胞界面中的积累，发现它们的积累发生在cSMAC形成后，可能是由于膜皱褶和/或内吞作用。这些结果表明，脂筏控制蛋白质转运到膜，但不参与筏相关分子的聚集，因此，脂筏不作为T细胞活化的平台。
We studied the function of lipid rafts in generation and signaling of T-cell receptor microclusters (TCR-MCs) and central supramolecular activation clusters (cSMACs) at immunological synapse (IS). It has been suggested that lipid raft accumulation creates a platform for recruitment of signaling molecules upon T-cell activation. However, several lipid raft probes did not accumulate at TCR-MCs or cSMACs even with costimulation and the fluorescence resonance energy transfer (FRET) between TCR or LAT and lipid raft probes was not induced at TCR-MCs under the condition of positive induction of FRET between CD3 zeta and ZAP-70. The analysis of LAT mutants revealed that raft association is essential for the membrane localization but dispensable for TCR-MC formation. Careful analysis of the accumulation of raft probes in the cell interface revealed that their accumulation occurred after cSMAC formation, probably due to membrane ruffling and/or endocytosis. These results suggest that lipid rafts control protein translocation to the membrane but are not involved in the clustering of raft-associated molecules and therefore that the lipid rafts do not serve as a platform for T-cell activation.