Insights on the trafficking and retro-translocation of glycosphingolipid-binding bacterial toxins.
Insights on the trafficking and retro-translocation of glycosphingolipid-binding bacterial toxins.
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DOI：
10.3389/fcimb.2012.00051
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发表时间：
2012
影响因子：
5.7
通讯作者：
Massol R
中科院分区：
文献类型：
--
作者：
Cho JA;Chinnapen DJ;Aamar E;te Welscher YM;Lencer WI;Massol R
一些细菌毒素和病毒已经进化出结合哺乳动物鞘糖脂以进入细胞内部的能力，在那里它们可以利用细胞运输和蛋白质易位机制的内源性机制来引起毒性。霍乱毒素（CT）是研究得最好的例子之一，是霍乱中大量分泌性腹泻的毒力因子。CT通过与质膜上的单唾液酸四己糖神经节苷脂（GM 1神经节苷脂）结合进入宿主细胞，在质膜上通过高尔基体网络（TGN）逆行转运到内质网（ER）中。在ER中，CT的一部分，CT-A1多肽，被解折叠，然后通过劫持错误折叠蛋白质的ER相关降解途径（ERAD）的组分“逆向易位”到胞质溶胶中。CT-A1在胞质溶胶中迅速重折叠，从而避免了蛋白酶体的降解和诱导毒性。在这里，我们强调了我们对细菌AB 5毒素如何诱导疾病的理解的最新进展。我们强调了这些毒素使用鞘糖脂在细胞内运输的分子机制，特别注意细胞如何感知和分类脂质受体。我们还讨论了几个新的研究，解决机制的毒素展开的ER和CTA 1链的逆转录易位到胞质溶胶的机制。
Some bacterial toxins and viruses have evolved the capacity to bind mammalian glycosphingolipids to gain access to the cell interior, where they can co-opt the endogenous mechanisms of cellular trafficking and protein translocation machinery to cause toxicity. Cholera toxin (CT) is one of the best-studied examples, and is the virulence factor responsible for massive secretory diarrhea seen in cholera. CT enters host cells by binding to monosialotetrahexosylganglioside (GM1 gangliosides) at the plasma membrane where it is transported retrograde through the trans-Golgi network (TGN) into the endoplasmic reticulum (ER). In the ER, a portion of CT, the CT-A1 polypeptide, is unfolded and then “retro-translocated” to the cytosol by hijacking components of the ER associated degradation pathway (ERAD) for misfolded proteins. CT-A1 rapidly refolds in the cytosol, thus avoiding degradation by the proteasome and inducing toxicity. Here, we highlight recent advances in our understanding of how the bacterial AB5 toxins induce disease. We highlight the molecular mechanisms by which these toxins use glycosphingolipid to traffic within cells, with special attention to how the cell senses and sorts the lipid receptors. We also discuss several new studies that address the mechanisms of toxin unfolding in the ER and the mechanisms of CT A1-chain retro-translocation to the cytosol.
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影响因子：
--
作者：
Fagerquist CK;Sultan O
通讯作者：
Sultan O
影响因子：
3.3
作者：
Li, Shuyu;Spooner, Robert A.;Roberts, Lynne M.
通讯作者：
Roberts, Lynne M.
DOI：
10.2165/00139709-200322010-00006
发表时间：
2003-01-01
期刊：
Toxicological Reviews
影响因子：
--
作者：
Lord, Michael J.;Jolliffe, Nicholas A.;Roberts, Lynne M.
通讯作者：
Roberts, Lynne M.
影响因子：
3.3
作者：
Bernardi, Kaleena M.;Forster, Michele L.;Tsai, Billy
通讯作者：
Tsai, Billy
影响因子：
3.2
作者：
Dixit, Garima;Mikoryak, Carole;Draper, Rockford K.
通讯作者：
Draper, Rockford K.