Dyve Anne Berit, Bergan Jonas, Utskarpen Audrun, Sandvig Kirsten
Faculty Division The Norwegian Radium Hospital, Centre for Cancer Biomedicine, University of Oslo, 0316 Oslo, Norway.
Biochem Biophys Res Commun. 2009 Dec 4;390(1):109-14. doi: 10.1016/j.bbrc.2009.09.076. Epub 2009 Sep 24.
Sorting nexin 8 (SNX8) belongs to the sorting nexin protein family, whose members are involved in endocytosis and endosomal sorting and signaling. The function of SNX8 has so far been unknown. Here, we have investigated the role of SNX8 in intracellular transport of the bacterial toxin Shiga toxin (Stx) and the plant toxin ricin. After being endocytosed, these toxins are transported retrogradely from endosomes, via the Golgi apparatus and the endoplasmic reticulum (ER), into the cytosol, where they exert their toxic effect. Interestingly, our experiments show that SNX8 regulates the transport of Stx and ricin differently; siRNA-mediated knockdown of SNX8 significantly increased the Stx transport to the trans-Golgi network (TGN), whereas ricin transport was slightly inhibited. We also found that SNX8 colocalizes with early endosome antigen 1 (EEA1) and with retromer components, suggesting an endosomal localization of SNX8 and supporting our finding that SNX8 is involved in endosomal sorting.
分选连接蛋白8（SNX8）属于分选连接蛋白家族，其成员参与内吞作用、内体分选和信号传导。迄今为止，SNX8的功能尚不清楚。在此，我们研究了SNX8在细菌毒素志贺毒素（Stx）和植物毒素蓖麻毒素的细胞内运输中的作用。这些毒素被内吞后，从内体通过高尔基体和内质网（ER）逆向运输到细胞质中，在那里发挥其毒性作用。有趣的是，我们的实验表明，SNX8对Stx和蓖麻毒素运输的调节方式不同；siRNA介导的SNX8敲低显著增加了Stx向反式高尔基体网络（TGN）的运输，而蓖麻毒素的运输则略有抑制。我们还发现，SNX8与早期内体抗原1（EEA1）和retromer组分共定位，表明SNX8定位于内体，并支持我们关于SNX8参与内体分选的发现。
