PKC-e Regulates Vesicle Delivery and Focal Exocytosis for Efficient IgG-mediated Phagocytosis
PKC-e is required for membrane addition during IgG-mediated phagocytosis; its role in this process is ill-defined. High resolution imaging revealed that PKC-e exits the Golgi and enters phagosomes on vesicles that then fuse. TNF and PKC-e colocalize at the Golgi and on vesicles that enter the phagosome. Loss of PKC-e and TNF delivery upon nocodazole treatment confirmed vesicular transport on microtubules. That TNF+ vesicles are not delivered in macrophages from PKC-e null mice, or upon dissociation of the Golgi-associated pool of PKC-e, implicates Golgi-tethered PKC-e as a driver of Golgi-to-phagosome trafficking. Finally, we established that PKC-e's regulatory domain is sufficient for delivery of TNF+ vesicles to the phagosome. These studies reveal a novel role for PKC-e in focal exocytosis: its regulatory domain drives Golgi-derived vesicles to the phagosome while 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.