Takizawa P A, Yucel J K, Veit B, Faulkner D J, Deerinck T, Soto G, Ellisman M, Malhotra V
Department of Biology, University of California, San Diego, La Jolla 92093.
Cell. 1993 Jun 18;73(6):1079-90. doi: 10.1016/0092-8674(93)90638-7.
We have identified a novel natural metabolite, ilimaquinone (IQ), from sea sponges that causes Golgi membranes to break down completely in vivo into small vesicular structures (called vesiculated Golgi membranes [VGMs]). Under these conditions, transport of newly synthesized proteins from endoplasmic reticulum (ER) to the cis-Golgi-derived VGMs is unaffected; however, further transport along the secretory pathway is blocked. Upon removal of the drug, VGMs reassemble rapidly into a Golgi complex, and protein transport is restored. By employing a cell-free system that reconstitutes vesicular transport between successive Golgi cisternae, we provide evidence that the inhibition of protein transport by IQ is specifically due to an inhibition of transport vesicle formation. In addition, like brefeldin A (BFA), IQ treatment prevents the association of beta-COP and ADP-ribosylation factor to the Golgi membranes; however, unlike BFA treatment, there is no retrograde transport of Golgi enzymes into ER.
我们从海绵中鉴定出一种新型天然代谢产物——伊里马醌（IQ），它能在体内使高尔基体膜完全分解为小泡状结构（称为泡状高尔基体膜[VGMs]）。在这些条件下，新合成的蛋白质从内质网（ER）向顺式高尔基体衍生的VGMs的转运不受影响；然而，沿分泌途径的进一步转运被阻断。去除药物后，VGMs迅速重新组装成高尔基体复合体，蛋白质转运得以恢复。通过使用一种无细胞系统来重建连续高尔基体囊泡之间的囊泡转运，我们提供了证据表明IQ对蛋白质转运的抑制具体是由于对转运囊泡形成的抑制。此外，与布雷菲德菌素A（BFA）一样，IQ处理可阻止β-COP和ADP-核糖基化因子与高尔基体膜的结合；然而，与BFA处理不同的是，没有高尔基体酶逆向转运到内质网中。
