MECHANISM OF BREFELDIN A ACTION

布雷菲德菌素A（Brefeldin A，BFA）是一种真菌代谢产物，具有广泛的生物活性。 生物活性，包括抗真菌和抗肿瘤活性。 在过去的几年里，人们对其产生了极大的兴趣。 对细胞的影响，因为它已被发现有一个独特的能力， 干扰细胞中的囊泡运输。 在其影响中， 分散高尔基复合体，至少将其部分成分返回到 内质网（ER）。 BFA还可以防止新合成的 这些蛋白质被指定为细胞表面的蛋白质离开ER。 这 属性负责其完全阻止 将病毒抗原呈递给细胞毒性T淋巴细胞。 更好地 为了了解BFA的作用机制，我们将其结合到两个 荧光染料，并研究其细胞内定位。 两 偶联物保持了它们的生物活性， 定位于活的或固定的细胞中的ER和高尔基体复合体。 结合的BFA选择性分配到细胞内， 膜可能是由于它与脂质的相互作用，因为它是 通过洗涤剂提取脂质消除。 这些共轭是 第一染料结合ER和高尔基体复合体而不结合其它 突出的膜结合区室，并应证明是有用的， 活细胞中这些细胞器的探针。 BFA的相互作用 与ER和高尔基复合体膜可能是必不可少的 对囊泡运输的影响。

Brefeldin A (BFA) is a fungal metabolite with a broad range of biological activities, including antifugal and antitumor activities. In the past few years, there has been tremendous interest in its effects on cells, since it has been found to have a unique ability to interfere with vesicular trafficking in cells. Among its effects, it disperses Golgi complex, returning at least some of its components to the endoplasmic reticulum (ER). BFA also prevents newly synthesized proteins destined for the cell surface from leaving the ER. This property is responsible for its ability to completely block the presentation of viral antigens to cytotoxic T lymphocytes. To better understand the mechanism of BFA action, we conjugated it to two fluorescent dyes and studied its intracellular localization. Both conjugates maintained their biological activity and both specifically localized to the ER and Golgi complex in live or aldehyde-fixed cells. The selective partitioning of conjugated BFA into intracellular membranes is probably due to its interaction with lipids as it is abolished by detergent extraction of lipids. These conjugates are the first dyes that bind the ER and Golgi complex without binding other prominent membrane bound compartments and should prove useful as probes for these organelles in living cells. The interaction of BFA with the ER and Golgi complex membranes may be essential to its effects on vesicular trafficking.