The secretion inhibitor Exo2 perturbs trafficking of Shiga toxin between endosomes and the trans-Golgi network.
The secretion inhibitor Exo2 perturbs trafficking of Shiga toxin between endosomes and the trans-Golgi network.
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分泌抑制剂Exo2伴随着内体和跨性高尔基网络之间的志贺毒素的运输。
DOI：
10.1042/bj20080149
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发表时间：
2008-09-15
期刊：
影响因子：
--
通讯作者：
Roberts LM
中科院分区：
文献类型：
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作者：
Spooner RA;Watson P;Smith DC;Boal F;Amessou M;Johannes L;Clarkson GJ;Lord JM;Stephens DJ;Roberts LM
据报道，小分子抑制剂 Exo2 {4-羟基-3-甲氧基-(5,6,7,8-四氢[1]苯并噻吩并[2,3-d]嘧啶-4-基)肼-苯甲醛}可完全破坏哺乳动物细胞中的高尔基体并刺激高尔基体-ER（内质网）融合，类似于已充分表征的真菌毒素 BFA （布雷菲德菌素 A）。据报道，Exo2 不会影响 TGN（跨高尔基体网络）的完整性，也不影响糖脂结合霍乱毒素从 TGN 到 ER 腔的直接逆行运输。我们检查了 BFA 和 Exo2 的作用，发现这两种化合物在抑制顺行转运方面没有区别，并且这两种试剂都会显着破坏 HeLa 和 BS-C-1 细胞中 TGN 的形态。然而，与 BFA 不同，Exo2 不会诱导 TGN 和内体区室的管化和合并。此外，与其对霍乱毒素的作用相反，Exo2 显着干扰志贺毒素向内质网的输送。总之，这些结果表明 Exo2 的可能靶标在 TGN、高尔基体和早期内体子集的水平上起作用，因此 Exo2 为检查哺乳动物细胞中的膜运输提供了比 BFA 更具选择性的工具。
The small-molecule inhibitor Exo2 {4-hydroxy-3-methoxy-(5,6,7,8-tetrahydrol[1]benzothieno[2,3-d]pyrimidin-4-yl)hydraz-one benzaldehyde} has been reported to disrupt the Golgi apparatus completely and to stimulate Golgi–ER (endoplasmic reticulum) fusion in mammalian cells, akin to the well-characterized fungal toxin BFA (brefeldin A). It has also been reported that Exo2 does not affect the integrity of the TGN (trans-Golgi network), or the direct retrograde trafficking of the glycolipid-binding cholera toxin from the TGN to the ER lumen. We have examined the effects of BFA and Exo2, and found that both compounds are indistinguishable in their inhibition of anterograde transport and that both reagents significantly disrupt the morphology of the TGN in HeLa and in BS-C-1 cells. However, Exo2, unlike BFA, does not induce tubulation and merging of the TGN and endosomal compartments. Furthermore, and in contrast with its effects on cholera toxin, Exo2 significantly perturbs the delivery of Shiga toxin to the ER. Together, these results suggest that the likely target(s) of Exo2 operate at the level of the TGN, the Golgi and a subset of early endosomes, and thus Exo2 provides a more selective tool than BFA for examining membrane trafficking in mammalian cells.