COMPLETE VESICULATION OF GOLGI MEMBRANES AND INHIBITION OF PROTEIN-TRANSPORT BY A NOVEL SEA SPONGE METABOLITE, ILIMAQUINONE

COMPLETE VESICULATION OF GOLGI MEMBRANES AND INHIBITION OF PROTEIN-TRANSPORT BY A NOVEL SEA SPONGE METABOLITE, ILIMAQUINONE
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DOI:
10.1016/0092-8674(93)90638-7
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发表时间:
1993-06-18
期刊:
影响因子:
64.5
通讯作者:
MALHOTRA, V
MALHOTRA, V
中科院分区:
生物学1区
文献类型:
--
作者:
TAKIZAWA, PA;YUCEL, JK;MALHOTRA, V

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我们已经从海绵中鉴定出一种新的天然代谢物,伊利马喹酮(IQ),它能使高尔基膜在体内完全分解成小的囊泡结构(称为囊泡化高尔基膜[VGM])。在这些条件下,新合成的蛋白质从内质网(ER)到顺式高尔基体衍生的VGM的运输不受影响,但沿着分泌途径的进一步运输被阻止。一旦药物被移除,VGM就会迅速重组成高尔基复合体,蛋白质的运输就会恢复。通过使用一个无细胞系统来重构连续高尔基池之间的囊泡运输,我们提供的证据表明,IQ抑制蛋白质运输的具体原因是抑制运输囊泡的形成。此外,与布雷菲尔丁A(BFA)一样,IQ处理阻止了β-COP和ADP核糖化因子与高尔基体膜的联系;然而,与BFA处理不同的是,不存在高尔基体酶向内质网的逆行运输。
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.