Flotillin-2 modulates fas signaling mediated apoptosis after hyperoxia in lung epithelial cells.
Flotillin-2 modulates fas signaling mediated apoptosis after hyperoxia in lung epithelial cells.
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DOI：
10.1371/journal.pone.0077519
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Jin Y
中科院分区：
文献类型：
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作者：
Wei S;Moon HG;Zheng Y;Liang X;An CH;Jin Y
脂筏是细胞膜的亚结构域，具有独特的蛋白质组成和高浓度的胆固醇和鞘糖脂。筏蛋白被认为介导多种细胞过程，包括信号转导。然而，其细胞机制仍不清楚。 Caveolin-1（cav-1，小窝标记蛋白）被认为是细胞外基质 (ECM) 刺激和细胞内信号之间的交换机。 Flotillin-2/reggie-1(Flot-2) 是另一种普遍表达的筏蛋白，它定义了非凹坑筏微结构域（平面筏）。其细胞功能在很大程度上是未知的。我们的新研究表明，Flot-2 与 cav-1 结合，通过调节 Fas 途径在控制细胞死亡方面发挥重要作用。使用 Beas2B 上皮细胞，我们发现与 cav-1 相比，Flot-2 通过阻止 Fas 介导的死亡诱导信号复合物 (DISC) 形成来提供细胞保护，随后抑制 caspase-8 介导的外源性细胞凋亡。此外，Flot-2 通过调节 Bcl-2 家族并抑制细胞色素 C 从线粒体释放到细胞质，减少线粒体介导的内在细胞凋亡。 Flot-2 通过上调凋亡抑制剂 (IAP) 家族成员进一步调节常见的凋亡途径并抑制 caspase-3 激活。最后，Flot-2 与 cav-1 相互作用并限制其表达。综上所述，我们发现 Flot-2 可以保护细胞免受 Fas 诱导的细胞凋亡，并抵消 cav-1 的促细胞凋亡作用。因此，Flot-2 在细胞稳态和细胞存活中发挥着至关重要的作用，表明单个筏蛋白的不同作用。
Lipid rafts are subdomains of the cell membrane with distinct protein composition and high concentrations of cholesterol and glycosphingolipids. Raft proteins are thought to mediate diverse cellular processes including signal transduction. However, its cellular mechanisms remain unclear. Caveolin-1 (cav-1, marker protein of caveolae) has been thought as a switchboard between extracellular matrix (ECM) stimuli and intracellular signals. Flotillin-2/reggie-1(Flot-2) is another ubiquitously expressed raft protein which defines non-caveolar raft microdomains (planar raft). Its cellular function is largely uncharacterized. Our novel studies demonstrated that Flot-2, in conjunction with cav-1, played important functions on controlling cell death via regulating Fas pathways. Using Beas2B epithelial cells, we found that in contrast to cav-1, Flot-2 conferred cytoprotection via preventing Fas mediated death-inducing signaling complex (DISC) formation, subsequently suppressed caspase-8 mediated extrinsic apoptosis. Moreover, Flot-2 reduced the mitochondria mediated intrinsic apoptosis by regulating the Bcl-2 family and suppressing cytochrome C release from mitochondria to cytosol. Flot-2 further modulated the common apoptosis pathway and inhibited caspase-3 activation via up-regulating the members in the inhibitor of apoptosis (IAP) family. Last, Flot-2 interacted with cav-1 and limited its expression. Taken together, we found that Flot-2 protected cells from Fas induced apoptosis and counterbalanced the pro-apoptotic effects of cav-1. Thus, Flot-2 played crucial functions in cellular homeostasis and cell survival, suggesting a differential role of individual raft proteins.
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影响因子：
20.3
作者：
Guo, Yi-He;Hernandez, Irene;Weiler, Hartmut
通讯作者：
Weiler, Hartmut
影响因子：
3.6
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Gumbleton, M
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Fujimoto, T
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