Rab6 and Rab11 Regulate Chlamydia trachomatis Development and Golgin-84-Dependent Golgi Fragmentation

Abstract

Many intracellular pathogens that replicate in special membrane bound compartments exploit cellular trafficking pathways by targeting small GTPases, including Rab proteins. Members of the Chlamydiaceae recruit a subset of Rab proteins to their inclusions, but the significance of these interactions is uncertain. Using RNA interference, we identified Rab6 and Rab11 as important regulators of Chlamydia infections. Depletion of either Rab6 or Rab11, but not the other Rab proteins tested, decreased the formation of infectious particles. We further examined the interplay between these Rab proteins and the Golgi matrix components golgin-84 and p115 with regard to Chlamydia-induced Golgi fragmentation. Silencing of the Rab proteins blocked Chlamydia-induced and golgin-84 knockdown-stimulated Golgi disruption, whereas Golgi fragmentation was unaffected in p115 depleted cells. Interestingly, p115-induced Golgi fragmentation could rescue Chlamydia propagation in Rab6 and Rab11 knockdown cells. Furthermore, transport of nutrients to Chlamydia, as monitored by BODIPY-Ceramide, was inhibited by Rab6 and Rab11 knockdown. Taken together, our results demonstrate that Rab6 and Rab11 are key regulators of Golgi stability and further support the notion that Chlamydia subverts Golgi structure to enhance its intracellular development.

Vesicle-Associated Membrane Protein 4 and Syntaxin 6 Interactions at the Chlamydial Inclusion

“…Data in this study identify the first SNARE protein involved in sphingomyelin trafficking to the chlamydial inclusion; however, there are other proteins involved in vesicle fusion that have been demonstrated to play a role in chlamydial sphingomyelin acquisition, such as small GTPase Rab proteins, which are involved in vesicle formation and trafficking (65). Specifically, Rabs 6, 11, and 14 have been identified as important mediators of chlamydial sphingomyelin acquisition (66,67). Interestingly, the recruitment of Rab proteins is not conserved across chlamydial species (68)(69)(70); however, a unique facet of VAMP4's recruitment to the chlamydial inclusion is that it is not conserved across chlamydial species or even C. trachomatis serovars, implying that VAMP4 may be recruited only to LGVcontaining inclusions, potentially contributing to the more-invasive nature of LGV strains compared to the invasiveness of other C. trachomatis serovars.…”

In Contrast to Chlamydia trachomatis, Waddlia chondrophila Grows in Human Cells without Inhibiting Apoptosis, Fragmenting the Golgi Apparatus, or Diverting Post-Golgi Sphingomyelin Transport

“…The only molecular explanation that had been put forward (i.e., that it occurs through degradation of the Golgi apparatus matrix protein golgin-84 [34]) is probably not correct, since it is doubtful that golgin-84 is degraded in intact infected cells (26). However, Golgi apparatus fragmentation during chlamydial infection has been found to require Rab proteins (55) and is therefore likely linked to vesicular transport; Golgi apparatus fragmentation may even be a consequence of the redirection of post-Golgi vesicular transport to the inclusion. If that is the case, it is not surprising that both events (Golgi fragmentation and post-Golgi sphingomyelin transport to the bacteria) can be seen in Chlamydia infection but that neither is seen in Waddlia infection.…”

Role of Phosphatidylinositol 4-Phosphate (PI4P) and Its Binding Protein GOLPH3 in Hepatitis C Virus Secretion

“…The fragmentation of the Golgi in HCV correlates with the decrease in general secretory capacity of the infected cell but further implicates the organelle in important viral processes and hints toward sequestration of secretory components at sites of viral assembly. Golgi disruption and decrease in secretory capacity of host cells is a peculiar feature of many infectious agents such as Chlamydia, poliovirus, and rhinovirus 1A, where the Golgi membranes serve an important role in viral replication and morphogenesis (57)(58)(59)(60).…”