RER1 regulates lipid metabolism in monocytes and macrophages

Area of Science:

• Cell Biology
• Immunology
• Metabolism

Background:

• Retention in endoplasmic reticulum sorting receptor 1 (RER1) regulates protein transport and complex assembly.
• RER1 is involved in the TREM2-DAP12 immune receptor complex, impacting signaling and phagocytosis.
• The role of RER1 in immune cell metabolism was previously unknown.

Purpose of the Study:

• To investigate the role of RER1 in the lipid metabolism of monocytic and macrophage-like cells.
• To understand how RER1 deficiency affects cellular lipid content and gene expression.

Main Methods:

• Utilized THP-1 cells differentiated into monocytic and macrophage-like states.
• Performed comprehensive mass spectrometry for lipidomic analysis.
• Conducted RNA sequencing to analyze gene expression related to lipid metabolism.
• Employed western immunoblotting to confirm protein expression changes.

Main Results:

• RER1 deficiency caused significant accumulation of lipid droplets in both cell types.
• Mass spectrometry revealed complex alterations in cellular lipid metabolism and lipid droplet composition.
• RNA sequencing identified RER1's regulatory role in genes associated with lipid metabolism.
• Western immunoblotting confirmed RER1's impact on key lipid metabolism proteins.

Conclusions:

• RER1 plays a critical role in regulating lipid metabolism in monocytes and macrophages.
• RER1 deficiency disrupts normal lipid homeostasis, leading to lipid droplet accumulation.
• These findings highlight RER1 as a potential target for modulating immune cell metabolism.