PKC-ε regulates vesicle delivery and focal exocytosis for efficient IgG-mediated phagocytosis

Protein kinase C (PKC)-epsilon is required for membrane addition during IgG-mediated phagocytosis, but its role in this process is ill defined. Here, we performed high-resolution imaging, which reveals that PKC-epsilon exits the Golgi and enters phagosomes on vesicles that then fuse. TNF and PKC-epsilon colocalize at the Golgi and on vesicles that enter the phagosome. Loss of PKC-epsilon and TNF delivery upon nocodazole treatment confirmed vesicular transport on microtubules. That TNF+ vesicles were not delivered in macrophages from PKC-epsilon null mice, or upon dissociation of the Golgi-associated pool of PKC-epsilon, implies that Golgi-tethered PKC-epsilon is a driver of Golgi-to-phagosome trafficking. Finally, we established that the regulatory domain of PKC-epsilon is sufficient for delivery of TNF+ vesicles to the phagosome. These studies reveal a novel role for PKC-epsilon in focal exocytosis - its regulatory domain drives Golgi-derived vesicles to the phagosome, whereas catalytic activity is required for their fusion. This is one of the first examples of a PKC requirement for vesicular trafficking and describes a novel function for a PKC regulatory domain.

Automated summary

The research revealed the essential role of PKC-ε in IgG-mediated phagocytosis, showing that its regulatory domain drives vesicles from the Golgi to the phagosome, while catalytic activity is required for their fusion. This study represents one of the first examples of a PKC requirement for vesicular trafficking and describes a novel function for a PKC regulatory domain.