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 clathrinindependent
pathway into vesicles named GPIAP–
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 traffi cking
pathway between GEECs and LEs. We found that VacA
routing from GEECs to LEs required polymerized actin.
During this traffi cking, VacA was transferred from GEECs
to EEs associated with polymerized actin structures. The
CD2-associated protein (CD2AP), a docking protein implicated
in intracellular traffi cking, bridged the fi lamentous
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.