ER proteins (red) are found in early phagocytic structures (arrows).


New results from Etienne Gagnon, Michel Desjardins (Université de Montréal, Montreal, Canada), and colleagues finally explain how a macrophage cell produces enough membrane to engulf material as large as itself—it uses large contributions of membrane from the ER. This is the first demonstration that the ER can fuse with the plasma membrane (PM).

In a previous proteomics experiment, Desjardins' group found several ER-associated proteins in phagosome preparations. But their first thought was contamination, as phagocytosis is widely considered to be a function of the PM. “This was something from the textbooks we all did not question,” Desjardins says. “It was not our aim to challenge this idea.” However, the new immunogold and immunocytochemical experiments clearly showed a distribution of ER marker proteins such as calnexin and calreticulin throughout the phagosome membrane.

Inhibition of phagocytosis revealed direct contacts between the ER and the PM at the sites of engulfment, where the two membranes apparently fused. ER contribution occurred early in the process, as the markers were also seen on the phagocytic cup, a structure formed before the phagosome fully surrounds the material to be engulfed. The ER contributed to phagocytosis mediated by various receptors, and even when only small amounts of membrane were required, indicating that its contribution is a general phenomenon in macrophages.

Neutrophils, in contrast, did not use ER membrane for phagocytosis. Desjardins believes this may reflect the different strategies of the two cell types. The antigen-presenting function of macrophages would be enhanced by the entry of pathogens directly into the ER, where they could undergo controlled trimming and antigen presentation, by both MHC class I and II molecules, in a nonlytic environment. Because neutrophils function primarily to engulf and destroy pathogens rapidly, they may not have the need for an ER-mediated phagocytic system, and may use other membrane sources, such as azurophilic granules, instead. ▪


Gagnon, E., et al.