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

Autor: Mohamed Trebak, Ananya Murali, Michelle R. Lennartz, Anna E. D’Amico, Cheryl M. Zajd, Xuexin Zhang, Alexander C. Wong
Rok vydání: 2021
Předmět:
Zdroj: J Cell Sci
ISSN: 1477-9137
0021-9533
DOI: 10.1242/jcs.258886
Popis: Protein kinase C (PKC)-ε 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-ε exits the Golgi and enters phagosomes on vesicles that then fuse. TNF and PKC-ε colocalize at the Golgi and on vesicles that enter the phagosome. Loss of PKC-ε and TNF delivery upon nocodazole treatment confirmed vesicular transport on microtubules. That TNF+ vesicles were not delivered in macrophages from PKC-ε null mice, or upon dissociation of the Golgi-associated pool of PKC-ε, implies that Golgi-tethered PKC-ε is a driver of Golgi-to-phagosome trafficking. Finally, we established that the regulatory domain of PKC-ε is sufficient for delivery of TNF+ vesicles to the phagosome. These studies reveal a novel role for PKC-ε 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.This article has an associated First Person interview with the first author of the paper.
Databáze: OpenAIRE