Chlamydia Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex Positioning

Abstract

The intracellular bacterium Chlamydia trachomatis develops in a parasitic compartment called the inclusion. Posttranslationally modified microtubules encase the inclusion, controlling the positioning of Golgi complex fragments around the inclusion. The molecular mechanisms by which Chlamydia coopts the host cytoskeleton and the Golgi complex to sustain its infectious compartment are unknown. Here, using a genetically modified Chlamydia strain, we discovered that both posttranslationally modified microtubules and Golgi complex positioning around the inclusion are controlled by the chlamydial inclusion protein CT813/CTL0184/InaC and host ARF GTPases. CT813 recruits ARF1 and ARF4 to the inclusion membrane, where they induce posttranslationally modified microtubules. Similarly, both ARF isoforms are required for the repositioning of Golgi complex fragments around the inclusion. We demonstrate that CT813 directly recruits ARF GTPases on the inclusion membrane and plays a pivotal role in their activation. Together, these results reveal that Chlamydia uses CT813 to hijack ARF GTPases to couple posttranslationally modified microtubules and Golgi complex repositioning at the inclusion.

Engineering yeast endosymbionts as a step toward the evolution of mitochondria

“…S4) and transformed it into E. coli ΔthiC::gfp-kan R cells. CT_813 is proposed to recruit ADP ribosylation factor GTPases and induce rearrangement of microtubules and Golgi around the Chlamydia inclusions (26). Fusions with S. cerevisiae cox2-60 cells again yielded yeast colonies growing on nonfermentable growth medium, but this time we did not observe E. coli colonies on the plates.…”

“…Therefore, it is possible that IncA may protect a membrane compartment against lysosomal degradation by interfering with yeast SNARE fusion function. CT_813 recruits ADP ribosylation factor GTPases and induces rearrangement of microtubules and Golgi around Chlamydia inclusions (26), processes which are proposed to play an important role in establishment of the replicative niche and may also play a role in establishing the yeast-E. coli endosymbiont. Further studies are required to define the precise roles of these SNARE-like proteins in establishing a stable yeast endosymbiont, as well as their potential relationship to the genetic elements that facilitated the establishment of stable endosymbionts within archaeal hosts.…”

IncV, a FFAT motif-containing Chlamydia protein, tethers the endoplasmic reticulum to the pathogen-containing vacuole

“…However, it is unknown if Inc proteins can also act as structural components to bring and maintain the ER and the inclusion membrane in close apposition. C. trachomatis encodes more than 50 putative Incs and only some of them have known functions in C. trachomatis infection (24,28,(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43). Recently, Mirrashidi et al (37) determined the Inc-human interactome from uninfected cells expressing C. trachomatis Inc proteins.…”

Safe haven under constant attack-TheChlamydia-containing vacuole

“…The small GTPase Arf1 and its guanine nucleotide exchange factor GBF1 regulate vesicle formation and transport at the Golgi. Both are also associated with the chlamydial inclusion, and Arf1 recruitment to the inclusion depends on the chlamydial effector CT813/InaC (Figure ; Kokes et al, ; Moorhead et al, ; Wesolowski et al, ). Depletion of GBF1 negatively affects inclusion expansion and stability but has no impact on chlamydial replication (Elwell et al, ).…”