Intracellular lipopolysaccharide binds RETREG1/FAM134B to regulate ER remodeling upon bacterial infection

Area of Science:

• Cell Biology
• Immunology
• Microbiology

Background:

• Selective autophagy of the endoplasmic reticulum (ER), known as ERphagy, is crucial for cellular homeostasis.
• The regulation of ERphagy during Gram-negative bacterial infections and its impact on host defense are not fully understood.

Purpose of the Study:

• To investigate the role of ERphagy in host responses to Gram-negative bacterial infection.
• To elucidate the mechanism by which bacterial components trigger ERphagy.

Main Methods:

• Affinity-isolation assays to identify bacterial-host protein interactions.
• Microscopy techniques to visualize ER fragments and bacterial localization.
• Bacterial infection models using *Salmonella enterica* serovar Typhimurium.

Main Results:

• *Salmonella* lipopolysaccharide (LPS) directly binds to the ER-resident receptor RETREG1/FAM134B.
• LPS binding induces RETREG1 oligomerization, ER membrane fragmentation, and subsequent bacterial clearance.
• Bacteria utilize outer membrane vesicles (OMVs) to deliver LPS into the host cytosol, activating ERphagy.

Conclusions:

• Gram-negative bacterial LPS triggers host ERphagy via RETREG1 activation.
• This ERphagy response promotes xenophagy and enhances antibacterial defense.
• The study reveals a novel mechanism of host-pathogen interaction involving ER remodeling.