BiP negatively affects ricin transport.
BiP negatively affects ricin transport.
复制标题
DOI：
10.3390/toxins5050969
复制
发表时间：
2013-05-10
期刊：
影响因子：
4.2
通讯作者：
Sandvig K
中科院分区：
文献类型：
--
作者：
Gregers TF;Skånland SS;Wälchli S;Bakke O;Sandvig K
AB植物毒素蓖麻毒素通过其B亚基与细胞表面的糖蛋白和糖脂结合。结合后，蓖麻毒素被内吞，然后通过高尔基体逆行运输到内质网(ER)。在内质网中，A亚单位在伴侣依赖的过程中被逆转到胞浆中，这一过程尚未得到充分探索。最近，两个单独的siRNA筛选表明，ER伴侣与蓖麻毒素毒性有关。内质网相关降解(ERAD)涉及错误折叠的蛋白质从内质网到胞浆的移位，可以想象蛋白质毒素利用这一途径。内质网伴侣蛋白Bip是一种重要的内质网调节因子，与霍乱和志贺毒素介导的毒性有关。在这项研究中，我们研究了Bip在蓖麻毒素转运到胞浆中的作用。我们首先证明了Bip的过表达抑制了蓖麻毒素的转位，并保护了细胞免受毒素的攻击。此外，shRNA介导的BiP耗尽增强了毒素易位，导致了更高的细胞毒性。BIP对蓖麻毒素毒性的抑制作用与内质网胁迫无关。我们的发现表明，与志贺毒素所显示的相反，BiP的存在并不促进而是抑制了蓖麻毒素进入细胞质。
The AB plant toxin ricin binds both glycoproteins and glycolipids at the cell surface via its B subunit. After binding, ricin is endocytosed and then transported retrogradely through the Golgi to the endoplasmic reticulum (ER). In the ER, the A subunit is retrotranslocated to the cytosol in a chaperone-dependent process, which is not fully explored. Recently two separate siRNA screens have demonstrated that ER chaperones have implications for ricin toxicity. ER associated degradation (ERAD) involves translocation of misfolded proteins from ER to cytosol and it is conceivable that protein toxins exploit this pathway. The ER chaperone BiP is an important ER regulator and has been implicated in toxicity mediated by cholera and Shiga toxin. In this study, we have investigated the role of BiP in ricin translocation to the cytosol. We first show that overexpression of BiP inhibited ricin translocation and protected cells against the toxin. Furthermore, shRNA-mediated depletion of BiP enhanced toxin translocation resulting in increased cytotoxicity. BiP-dependent inhibition of ricin toxicity was independent of ER stress. Our findings suggest that in contrast to what was shown with the Shiga toxin, the presence of BiP does not facilitate, but rather inhibits the entry of ricin into the cytosol.
登录
查看更多内容
影响因子：
3.3
作者：
Li, Shuyu;Spooner, Robert A.;Roberts, Lynne M.
通讯作者：
Roberts, Lynne M.
影响因子：
11.8
作者：
Moreau, Dimitri;Kumar, Pankaj;Bard, Frederic
通讯作者：
Bard, Frederic
影响因子：
2.2
作者：
Klasen, M;Spillmann, FJX;Wabl, M
通讯作者：
Wabl, M
影响因子：
11.8
作者：
Shen, JS;Chen, X;Prywes, R
通讯作者：
Prywes, R
影响因子：
4.8
作者：
Shen, JS;Prywes, R
通讯作者：
Prywes, R