Neutralizing Monoclonal Antibodies against Disparate Epitopes on Ricin Toxin's Enzymatic Subunit Interfere with Intracellular Toxin Transport.
Neutralizing Monoclonal Antibodies against Disparate Epitopes on Ricin Toxin's Enzymatic Subunit Interfere with Intracellular Toxin Transport.
复制标题
针对蓖麻毒素酶亚基上不同表位的中和单克隆抗体会干扰细胞内毒素转运。
DOI：
10.1038/srep22721
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发表时间：
2016
影响因子：
4.6
通讯作者：
Mantis,NicholasJ
中科院分区：
文献类型：
--
作者：
Yermakova,Anastasiya;Klokk,ToveIrene;O'Hara,JoanneM;Cole,Richard;Sandvig,Kirsten;Mantis,NicholasJ
蓖麻毒素是细菌和植物毒素的A-B家族的成员，其利用逆行运输到高尔基体和内质网（ER）作为将其细胞毒性酶亚基递送到哺乳动物细胞的细胞质中的手段。在这项研究中，我们证明，R70和SyH 7，两个良好的特点是单克隆抗体（mAb）针对不同的表位表面上的蓖麻毒素的酶亚基（RTA），干扰毒素运输从质膜到高尔基体网络。在细胞表面形成的毒素-mAb复合物延迟蓖麻毒素从EEA-1+和Rab 7+囊泡中排出，并增强毒素在LAMP-1+囊泡中的积累，表明复合物注定在溶酶体中降解。其他三个RTA特异性中和单克隆抗体对不同的表位是相似的R70和SyH 7的蓖麻毒素逆行转运的影响。我们得出结论，干扰毒素逆行转运可能是针对RTA上不同表位的毒素中和抗体的标志。
Ricin is a member of the A-B family of bacterial and plant toxins that exploit retrograde trafficking to the Golgi apparatus and endoplasmic reticulum (ER) as a means to deliver their cytotoxic enzymatic subunits into the cytoplasm of mammalian cells. In this study we demonstrate that R70 and SyH7, two well-characterized monoclonal antibodies (mAbs) directed against distinct epitopes on the surface of ricin’s enzymatic subunit (RTA), interfere with toxin transport from the plasma membrane to the trans Golgi network. Toxin-mAb complexes formed on the cell surface delayed ricin’s egress from EEA-1+and Rab7+vesicles and enhanced toxin accumulation in LAMP-1+vesicles, suggesting the complexes were destined for degradation in lysosomes. Three other RTA-specific neutralizing mAbs against different epitopes were similar to R70 and SyH7 in terms of their effects on ricin retrograde transport. We conclude that interference with toxin retrograde transport may be a hallmark of toxin-neutralizing antibodies directed against disparate epitopes on RTA.