Exo1: A new chemical inhibitor of the exocytic pathway
Exo1: A new chemical inhibitor of the exocytic pathway
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DOI：
10.1073/pnas.0631766100
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发表时间：
2003-05-27
影响因子：
11.1
通讯作者：
Kirchhausen, T
中科院分区：
文献类型：
--
作者：
Feng, Y;Yu, S;Kirchhausen, T
使用表型筛选来搜索可以干扰膜运输中的特定步骤的药物样分子。在该筛选中鉴定的2-（4-氟苯甲酰氨基）-苯甲酸甲酯（Exo 1）诱导高尔基体快速塌陷至内质网，从而急性抑制从内质网发出的运输。与Brefeldin A（BFA）一样，Exo 1诱导ADP-核糖基化因子（ARIF）1从高尔基体膜快速释放，但对trans-Golgi网络的组织影响较小。我们的数据表明，Exo 1的行为从BFA不同的机制。与BFA不同，Exo 1不会诱导CtBP/Bars 50的ADP-核糖基化，也不会干扰高尔基体ARF特异性鸟嘌呤核苷酸交换因子的活性。因此，在控制高尔基体微管的过程中，Exo 1允许Bars 50的脂肪酸交换活性与ARF 1活性区分开来。
A phenotypic screen was used to search for drug-like molecules that can interfere with specific steps in membrane traffic. 2-(4-Fluorobenzoylamino)-benzoic acid methyl ester (Exo1), identified in this screen, induces a rapid collapse of the Golgi to the endoplasmic reticulum, thus acutely inhibiting the traffic emanating from the endoplasmic reticulum. Like Brefeldin A (BFA), Exo1 induces the rapid release of ADP-ribosylation factor (ARIF) 1 from Golgi membranes but has less effect on the organization of the trans-Golgi network. Our data indicate that Exo1 acts by a different mechanism from BFA. Unlike BFA, Exo1 does not induce the ADP-ribosylation of CtBP/Bars50 and does not interfere with the activity of guanine nucleotide exchange factors specific for Golgi-based ARFs. Thus, Exo1 allows the fatty acid exchange activity of Bars50 to be distinguished from ARF1 activity in the control of Golgi tubulation.