Intracellular Trafficking of Clostridium perfringens Iota-Toxin b
Intracellular Trafficking of Clostridium perfringens Iota-Toxin b
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DOI：
10.1128/iai.00483-12
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发表时间：
2012-10-01
影响因子：
3.1
通讯作者：
Sakurai, Jun
中科院分区：
文献类型：
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作者：
Nagahama, Masahiro;Umezaki, Mariko;Sakurai, Jun
产气荚膜梭菌i毒素由酶组分（Ia）和结合组分（Ib）组成。Ib与细胞表面受体结合，在脂筏中发生寡聚化，并结合Ia。然后将所得复合物内吞。在这里，我们展示了iota毒素的细胞内运输。Ib单体在4 ℃与细胞结合后，Ib的寡聚体在37 ℃形成，随后消失。Ib的免疫荧光染色显示内化的Ib被转运到早期的内体。一部分Ib通过再循环内体返回质膜，而其余的则转运到晚期内体和溶酶体降解。降解的Ib通过Ib引起的细胞内Ca 2+浓度的增加而被递送到质膜。巴弗洛霉素A1，一种内体酸化抑制剂，引起Ib在内体中的积累，诺考达唑和秋水仙碱，微管破坏剂，限制Ib在胞质溶胶中的运动。这些结果表明，内化的Ia和Ib复合物被递送到早期内体，随后Ia递送到细胞质主要发生在早期内体中。Ib通过再循环内体被送回质膜或转运到晚期内体和溶酶体降解。降解的Ib被运输到质膜。
Clostridium perfringens iota-toxin is composed of an enzymatic component (Ia) and a binding component (Ib). Ib binds to a cell surface receptor, undergoes oligomerization in lipid rafts, and binds Ia. The resulting complex is then endocytosed. Here, we show the intracellular trafficking of iota-toxin. After the binding of the Ib monomer with cells at 4 degrees C, oligomers of Ib formed at 37 degrees C and later disappeared. Immunofluorescence staining of Ib revealed that the internalized Ib was transported to early endosomes. Some Ib was returned to the plasma membrane through recycling endosomes, whereas the rest was transported to late endosomes and lysosomes for degradation. Degraded Ib was delivered to the plasma membrane by an increase in the intracellular Ca2+ concentration caused by Ib. Bafilomycin A1, an endosomal acidification inhibitor, caused the accumulation of Ib in endosomes, and both nocodazole and colchicine, microtubule-disrupting agents, restricted Ib's movement in the cytosol. These results indicated that an internalized Ia and Ib complex was delivered to early endosomes and that subsequent delivery of Ia to the cytoplasm occurs mainly in early endosomes. Ib was either sent back to the plasma membranes through recycling endosomes or transported to late endosomes and lysosomes for degradation. Degraded Ib was transported to plasma membranes.