Brefeldin A: insights into the control of membrane traffic and organelle structure.
Brefeldin A: insights into the control of membrane traffic and organelle structure.
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DOI：
10.1083/jcb.116.5.1071
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发表时间：
1992-03
期刊：
影响因子：
--
通讯作者：
Lippincott-Schwartz J
中科院分区：
文献类型：
--
作者：
Klausner RD;Donaldson JG;Lippincott-Schwartz J
在过去的一百年里，细胞器的定义在很大程度上是由形态学观察推动的，但最近已经被功能和生化研究补充和补充（Palade, 1975）。因此，细胞器现在通过它们的形态和组成它们的一组成分来识别。确定细胞器的身份是如何建立和维持的，以及新合成的蛋白质和膜如何被分类到不同的细胞器是细胞器发生的核心问题。在中央空泡系统（由内质网、高尔基体、分泌囊泡、内体和溶酶体组成）内发生的许多细胞功能的关键是膜运输，它介导不同细胞器之间成分的交换。膜交通有两个关键特征。首先，只有特定的细胞器交换膜，这种交换的模式定义了所谓的膜途径。第二，多条通路在中央空泡系统的特定点相交。为了让特定的组分在这样的交叉点上“选择”正确的路径，存在将选择强加于特定分子的机制。这个过程被称为排序。中央液泡系统内每个细胞器的特性可能与膜交通的特性密切相关。进入和离开细胞器的膜量的不平衡会对隔室的大小产生深远的影响。此外，分类失败或靶向途径的畸变预计会深刻影响单个细胞器的身份。最近，利用一种特殊的药物brefeldin A （BFA）研究了膜交通的控制与细胞器结构的维持之间的关系。在这篇综述中，我们将总结BFA的最新发现，并提出一些关于中央液泡系统内膜运输的机制和调节的推测模型。
THE definition of cellular organelles has evolved over the last hundred years largely driven by morphologic observations, but more recently has been supplemented and complemented by functional and biochemical studies (Palade, 1975). Thus, organelles are now identified both by their morphology and by the set ofcomponents that comprise them. Determining how organelle identity is established and maintained and how newly synthesized protein and membrane are sorted to different organelles are the central issues of organellogenesis. Essential to the many cellular functions that take place within the central vacuolar system (which consists ofthe ER, Golgi apparatus, secretory vesicles, endosomes, and lysosomes) is membrane traffic which mediates the exchange of components between different organelles. There are two critical characteristics of membrane traffic. First, only certain sets oforganelles exchange membrane and the patterns of this exchange define what are called membrane pathways. Second, multiple pathways intersect at specific points within the central vacuolar system. For specific components to" choose" the correct pathway at such points of crossing, mechanisms exist to impose choices on specific molecules. This process is called sorting. The characteristics of each organelle within the central vacuolar system are likely to be intimately tied to the properties of membrane traffic. An imbalance in the magnitude of membrane input into and egress from an organelle would have profound effects on the size ofthat compartment. In addition, failures in sorting or aberrations in targeting pathways would be expected to profoundly affect the identity of individual organelles. Recently, the relationship between the control of membrane traffic and the maintenance of organelle structure has been investigated with the use ofa remarkable drug, brefeldin A (BFA).'In this review we will summarize recent findings with BFA and propose some speculative models concerning the mechanism and regulation ofmembrane traffic within the central vacuolar system.