Differential use of endoplasmic reticulum membrane for phagocytosis in J774 macrophages

Area of Science:

• Cell Biology
• Immunology
• Membrane Trafficking

Background:

• Phagocytosis is crucial for cellular defense and requires continuous membrane supply.
• Endocytic compartments typically provide membrane for phagosome formation.
• Previous studies suggested endoplasmic reticulum (ER) membrane can contribute to phagocytosis, but the mechanism was unknown.

Purpose of the Study:

• To elucidate the molecular mechanism of ER-plasma membrane fusion during phagocytosis.
• To identify the specific proteins involved in ER membrane contribution to phagosomes.
• To understand how macrophages utilize intracellular membrane sources during phagocytosis.

Main Methods:

• Investigated ER-plasma membrane fusion in J774 macrophages during phagocytosis of particles of varying sizes.
• Utilized genetic and biochemical approaches to identify key proteins involved in the fusion process.
• Focused on the role of ER-resident soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins.

Main Results:

• Direct ER-plasma membrane fusion during phagocytosis is dependent on the ER-resident SNARE protein ERS24/Sec22b.
• J774 macrophages activate this ER-plasma membrane fusion mechanism specifically when engulfing large particles (3.0 µm).
• This fusion allows macrophages to access the abundant membrane reserves of the ER.

Conclusions:

• ERS24/Sec22b is essential for ER-plasma membrane fusion during phagocytosis.
• Macrophages employ a size-dependent mechanism to recruit ER membrane for phagosome formation.
• This finding reveals a novel pathway for membrane supply during phagocytosis, utilizing the ER as a primary source.