SPOTS: signaling protein oligomeric transduction structures are early mediators of death receptor-induced apoptosis at the plasma membrane.
SPOTS: signaling protein oligomeric transduction structures are early mediators of death receptor-induced apoptosis at the plasma membrane.
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斑点：信号蛋白寡聚转导结构是质膜上死亡受体诱导的凋亡的早期介体。
DOI：
10.1083/jcb.200406101
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发表时间：
2004-11-22
影响因子：
7.8
通讯作者：
Lenardo, Michael J
中科院分区：
文献类型：
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作者：
Siegel, Richard M;Muppidi, Jagan R;Sarker, Malabika;Lobito, Adrian;Jen, Melinda;Martin, David;Straus, Stephen E;Lenardo, Michael J
Fas(CD95，APO-1，TNFRSF6)是一个肿瘤坏死因子受体超家族成员，直接触发细胞凋亡，有助于维持淋巴细胞稳态，预防自身免疫。虽然FADD和caspase-8已被确定为Fas信号转导的关键细胞内介质，但尚不清楚这些蛋白如何募集到Fas死亡结构域而导致受体信号复合体中caspase-8的激活。我们使用高分辨率共聚焦显微镜和活细胞成像来研究Fas信号转导的早期事件的后遗症。这些研究揭示了Fas信号转导的一个新阶段，在这个阶段，受体连接导致表面受体寡聚体的形成，我们称之为信号蛋白寡聚转导结构(SPOTS)。斑点的形成依赖于完整的Fas死亡结构域和FADD的存在，但与caspase活性无关。对自身免疫淋巴增殖性综合征(ALPS)患者表达Fas突变的细胞的分析表明，ALPS中斑点的形成可以通过不同的机制来破坏。
Fas (CD95, APO-1, TNFRSF6) is a TNF receptor superfamily member that directly triggers apoptosis and contributes to the maintenance of lymphocyte homeostasis and prevention of autoimmunity. Although FADD and caspase-8 have been identified as key intracellular mediators of Fas signaling, it is not clear how recruitment of these proteins to the Fas death domain leads to activation of caspase-8 in the receptor signaling complex. We have used high-resolution confocal microscopy and live cell imaging to study the sequelae of early events in Fas signaling. These studies have revealed a new stage of Fas signaling in which receptor ligation leads to the formation of surface receptor oligomers that we term signaling protein oligomerization transduction structures (SPOTS). Formation of SPOTS depends on the presence of an intact Fas death domain and FADD but is independent of caspase activity. Analysis of cells expressing Fas mutations from patients with the autoimmune lymphoproliferative syndrome (ALPS) reveals that formation of SPOTS can be disrupted by distinct mechanisms in ALPS.