Calcium waves bypass the phagosome in FcγRIIA mutants.


Phagolysosome fusion is a calcium dependent process. Now, Randall Worth and colleagues (University of Pennsylvania School of Medicine, Philadelphia, PA), and Howard Petty and colleagues (University of Michigan School of Medicine, Ann Arbor, MI) find that a three amino acid motif in the IgG receptor FcγRIIA causes a calcium wave traveling along the plasma membrane to split in two, with one part sweeping over the phagosome surface. Mutation of the LTL sequence, prevents wave bifurcation and inhibits phagolysosome fusion.Using high speed imaging techniques, the authors can watch the calcium wave move around the plasma membrane after phagocytosis. As the wave approaches the phagosome, it splits in two with part of the wave crossing a bridge formed by a thread of ER that connects the plasma membrane and the phagosome.

This ER thread has been seen before in electron micrographs, but its function was unclear. “We've seen the signal moving between the two organelles and the thread would account for it,” says Petty. He speculates that the LTL sequence forms part of a super-molecular aggregate between the plasma membrane, the ER, and the phagosome. When it is mutated the complex fails to form, the bridge is not built, and the calcium wave continues along the plasma membrane, ignoring the phagosome. And since calcium is a major trigger for membrane fusion, it fits with the model that phagolysosome fusion is impaired in the mutants. ▪


Worth, R.G., et al. PNAS. 10.1073/pnas.0836650100.