The membrane organization of leukotriene synthesis
The membrane organization of leukotriene synthesis
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DOI：
10.1073/pnas.0308523101
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发表时间：
2004-04-27
影响因子：
11.1
通讯作者：
Soberman, RJ
中科院分区：
文献类型：
--
作者：
Mandal, AK;Skoch, J;Soberman, RJ
导致白三烯（LT）C-4形成的细胞信号传导需要四种关键生物合成酶在外核膜和内质网上的定位。这些蛋白质是否存在任何大分子组织尚不清楚。通过使用荧光寿命成像显微镜和生化分析，我们证明了存在两个不同的多聚体复合物，调节LT在RBL-2 H3细胞的形成。一种复合物由LTC 4合酶和5-脂氧合酶激活蛋白（FLAP）的多聚体组成。第二个复合体由FLAP的多聚体组成。令人惊讶的是，所有的LTC 4合酶被发现与FLAP。结果表明，LTC 4和LTB 4的形成可能是由生物合成酶在离散分子复合物中的区室化决定的。
Cell signaling leading to the formation of leukotriene (LT)C-4 requires the localization of the four key biosynthetic enzymes on the outer nuclear membrane and endoplasmic reticulum. Whether any macromolecular organization of these proteins exists is unknown. By using fluorescence lifetime imaging microscopy and biochemical analysis, we demonstrate the presence of two distinct multimeric complexes that regulate the formation of LTs in RBL-2H3 cells. One complex consists of multimers of LTC4 synthase and the 5-lipoxy-genase activating protein (FLAP). The second complex consists of multimers of FLAP. Surprisingly, all LTC4 synthase was found to be in association with FLAP. The results indicate that the formation of LTC4 and LTB4 may be determined by the compartmentalization of biosynthetic enzymes in discrete molecular complexes.