Early endosomes associated with dynamic F-actin structures are required for late trafficking of H. pylori VacA toxin.
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.
Gauthier
Nils C
NC
Unité 627 and 2Unité 568, Institut National de la Santé et de la Recherche Medicale, Faculty of Medicine, 06107 Nice, Cedex 02, France.
Monzo
Pascale
P
Gonzalez
Teresa
T
Doye
Anne
A
Oldani
Amanda
A
Gounon
Pierre
P
Ricci
Vittorio
V
Cormont
Mireille
M
Boquet
Patrice
P
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006367:HeLa Cells; D016480:Helicobacter pylori / Q000737:chemistry*; D006801:Humans; D021381:Protein Transport
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D001426:Bacterial Proteins; C114545:CD2-associated protein; D003598:Cytoskeletal Proteins; D017261:Glycosylphosphatidylinositols; C074689:VacA protein, Helicobacter pylori