Early endosomes associated with dynamic F-actin structures are required for late trafficking of H. pylori VacA toxin.
Early endosomes associated with dynamic F-actin structures are required for late trafficking of H. pylori VacA toxin.
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DOI：
10.1083/jcb.200609061
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发表时间：
2007-04-23
期刊：
影响因子：
--
通讯作者：
Boquet P
中科院分区：
文献类型：
--
作者：
Gauthier NC;Monzo P;Gonzalez T;Doye A;Oldani A;Gounon P;Ricci V;Cormont M;Boquet P
糖基磷脂酰肌醇锚定蛋白（GPI-AP）通过网格蛋白非依赖性途径被内吞到称为GPI-AP富集早期内体区室（GEEC）的囊泡中。我们最近表明，由幽门螺杆菌分泌的空泡毒素VacA被内吞到GEEC中（Gauthier，N.C.，P. Monzo，V. Kaddai，A. Doye，V. Ricci，and P. Boquet. 2005.摩尔生物细胞16：4852-4866）。与GPI-AP主要回收回质膜不同，VacA到达早期内体（EE），然后到达晚期内体（LE），在那里发生空泡化。在本研究中，我们使用VacA来研究GEECs和LEs之间的运输途径。我们发现，VacA路由从GEEC LE需要聚合肌动蛋白。在这种运输过程中，VacA从GEEC转移到与聚合肌动蛋白结构相关的EE。CD 2相关蛋白（CD 2AP）是一种参与细胞内运输的对接蛋白，它将丝状肌动蛋白（F-actin）结构与含有VacA的EE连接起来。CD 2AP调节这些F-actin结构，并且需要将VacA从GEEC转移到LE。这些结果表明，从GEEC到LE的分选需要EE上的动态F-肌动蛋白结构。
Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are endocytosed by a clathrin- independent pathway into vesicles named GPI-AP–enriched early endosomal compartments (GEECs). We recently showed that the vacuolating toxin VacA secreted by Helicobacter pylori is endocytosed into the GEECs (Gauthier, N.C., P. Monzo, V. Kaddai, A. Doye, V. Ricci, and P. Boquet. 2005. Mol. Biol. Cell. 16:4852–4866). Unlike GPI-APs that are mostly recycled back to the plasma membrane, VacA reaches early endosomes (EEs) and then late endosomes (LEs), where vacuolation occurs. In this study, we used VacA to study the trafficking pathway between GEECs and LEs. We found that VacA routing from GEECs to LEs required polymerized actin. During this trafficking, VacA was transferred from GEECs to EEs associated with polymerized actin structures. The CD2-associated protein (CD2AP), a docking protein implicated in intracellular trafficking, bridged the filamentous actin (F-actin) structures with EEs containing VacA. CD2AP regulated those F-actin structures and was required to transfer VacA from GEECs to LEs. These results demonstrate that sorting from GEECs to LEs requires dynamic F-actin structures on EEs.
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