Interactions between the Coxiella burnetii parasitophorous vacuole and the endoplasmic reticulum involve the host

Anna V Justis1, Bryan Hansen2, Paul A Beare3

  • 1Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.

Cellular Microbiology
|June 28, 2016
PubMed

Insights

Coxiella burnetii infection hijacks host cell processes by recruiting oxysterol-binding protein-related protein 1 long (ORP1L) to its vacuole. This protein is crucial for maintaining the vacuole

Area of Science:

  • Microbiology
  • Cell Biology
  • Host-Pathogen Interactions

Background:

  • Coxiella burnetii, an intracellular bacterium, requires a specialized vacuole for replication.
  • Host cell lipids are vital for this vacuole, but Coxiella's manipulation mechanisms are unclear.
  • Oxysterol-binding protein-related protein 1 long (ORP1L) impacts endocytic trafficking and ER-endosome interactions.

Purpose of the Study:

  • To investigate the role of ORP1L in Coxiella burnetii infection.
  • To determine how ORP1L interacts with the Coxiella parasitophorous vacuole (PV).

Main Methods:

  • Tracking ORP1L localization during infection using microscopy.
  • Employing the Coxiella Dot/Icm secretion system for effector protein delivery.
  • Utilizing electron microscopy to visualize membrane contacts.
  • Depleting ORP1L to assess its impact on PV size.

Main Results:

  • ORP1L rapidly localized to the Coxiella PV via the Dot/Icm system.
  • ORP1L's ankyrin repeats mediated PV binding, suggesting interaction with a PV protein.
  • ORP1L co-localized with the ER at the PV, forming membrane contact sites.
  • ORP1L depletion resulted in significantly smaller PVs.

Conclusions:

  • ORP1L is recruited to the Coxiella PV by the bacterium.
  • ORP1L influences PV membrane dynamics and ER interactions.
  • ORP1L plays a key role in maintaining the intracellular niche for Coxiella replication.

Related Concept Videos

Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
5.4K
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
6.7K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
3.2K
Vesicular Tubular Clusters01:45

Vesicular Tubular Clusters

After budding out from the ER membrane, some COPII vesicles lose their coat and fuse with one another to form larger vesicles and interconnected tubules called vesicular tubular clusters or VTCs. These clusters constitute a compartment at the ER-Golgi interface known as ERGIC (Endoplasmic Reticulum Golgi Intermediate Compartment). The ERGIC is a mobile membrane-bound cargo transport system that sorts proteins secreted from ER and delivers them to the Golgi.
With the help of motor proteins such...
3.3K
COP Coated Vesicles00:59

COP Coated Vesicles

Membrane-enclosed structures called vesicles transport proteins and lipids across the cell. The vesicles derive their cargo from the plasma membrane, Golgi, ER, or endosome. Coated vesicles are spherical, protein-coated carriers with a 50–100 nm diameter that mediate bidirectional transport between the ER and the Golgi. The distribution of proteins between the ER and Golgi complex is dynamic and is maintained by different coated vesicles. Their formation is driven by the assembly of...
18.5K
Endoplasmic Reticulum01:39

Endoplasmic Reticulum

The Endoplasmic Reticulum (ER) in eukaryotic cells is a substantial network of interconnected membranes with diverse functions, from calcium storage to biomolecule synthesis. A primary component of the endomembrane system, the ER manufactures phospholipids critical for membrane function throughout the cell. Additionally, the two distinct regions of the ER specialize in the manufacture of specific lipids and proteins.
117.8K