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肉毒杆菌血凝素通过直接结合 E-钙黏蛋白破坏细胞间上皮屏障。

Botulinum hemagglutinin disrupts the intercellular epithelial barrier by directly binding E-cadherin.

机构信息

Laboratory for Infection Cell Biology, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.

出版信息

J Cell Biol. 2010 May 17;189(4):691-700. doi: 10.1083/jcb.200910119. Epub 2010 May 10.

DOI:10.1083/jcb.200910119
PMID:20457762
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2872904/
Abstract

Botulinum neurotoxin is produced by Clostridium botulinum and forms large protein complexes through associations with nontoxic components. We recently found that hemagglutinin (HA), one of the nontoxic components, disrupts the intercellular epithelial barrier; however, the mechanism underlying this phenomenon is not known. In this study, we identified epithelial cadherin (E-cadherin) as a target molecule for HA. HA directly binds E-cadherin and disrupts E-cadherin-mediated cell to cell adhesion. Although HA binds human, bovine, and mouse E-cadherin, it does not bind rat or chicken E-cadherin homologues. HA does not interact with other members of the classical cadherin family such as neural and vascular endothelial cadherin. Expression of rat E-cadherin but not mouse rescues Madin-Darby canine kidney cells from HA-induced tight junction (TJ) disruptions. These data demonstrate that botulinum HA directly binds E-cadherin and disrupts E-cadherin-mediated cell to cell adhesion in a species-specific manner and that the HA-E-cadherin interaction is essential for the disruption of TJ function.

摘要

肉毒杆菌神经毒素由肉毒梭菌产生，并通过与无毒成分的关联形成大型蛋白质复合物。我们最近发现，其中一种无毒成分血凝素 (HA) 会破坏细胞间上皮屏障；然而，这种现象的机制尚不清楚。在这项研究中，我们确定上皮钙黏蛋白 (E-cadherin) 是 HA 的靶分子。HA 可直接与 E-cadherin 结合并破坏 E-cadherin 介导的细胞间粘附。尽管 HA 结合人、牛和鼠 E-cadherin，但不结合大鼠或鸡 E-cadherin 同源物。HA 不与经典钙黏蛋白家族的其他成员（如神经和血管内皮钙黏蛋白）相互作用。表达大鼠 E-cadherin 而非小鼠可挽救 Madin-Darby 犬肾细胞免受 HA 诱导的紧密连接 (TJ) 破坏。这些数据表明，肉毒梭菌 HA 以物种特异性的方式直接与 E-cadherin 结合并破坏 E-cadherin 介导的细胞间粘附，并且 HA-E-cadherin 相互作用对于 TJ 功能的破坏是必不可少的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3e8/2872904/093f6cfdd150/JCB_200910119_RGB_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3e8/2872904/72b123c64fc2/JCB_200910119_RGB_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3e8/2872904/f957af3cdaee/JCB_200910119_RGB_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3e8/2872904/8c77f47d28b8/JCB_200910119_RGB_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3e8/2872904/1a86140095e5/JCB_200910119_RGB_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3e8/2872904/093f6cfdd150/JCB_200910119_RGB_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3e8/2872904/72b123c64fc2/JCB_200910119_RGB_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3e8/2872904/f957af3cdaee/JCB_200910119_RGB_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3e8/2872904/8c77f47d28b8/JCB_200910119_RGB_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3e8/2872904/1a86140095e5/JCB_200910119_RGB_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3e8/2872904/093f6cfdd150/JCB_200910119_RGB_Fig5.jpg

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