Abstract
During phagocytosis, internal membranes are recruited to the site of pathogen binding and fuse with the plasma membrane, providing the membrane needed for pseudopod extension and target uptake. The mechanism by which vesicles destined for the phagosome are generated, targeted, and fuse is unknown. We established that Golgi-associated protein kinase C-epsilon (PKC-ε) is necessary for the addition of membrane during FcyR-mediated phagocytosis. PKC-ε is tethered to the Golgi through interactions between its’ regulatory domain and the Golgi lipids PI4P and diacylglycerol; disruption of these interactions prevents PKC-ε concentration at phagosomes and decreases phagocytosis. The accumulated evidence suggests that PKC-ε orchestrates vesicle formation at the Golgi by a mechanism requiring lipid binding but not enzymatic activity. This review discusses how PKC-ε might mediate vesicle formation at the level of budding and fission. Specifically, we discuss PKC-ε binding partners, the formation of lipid subdomains to generate membrane curvature, and PKC-ε mediated links to the actin and microtubule cytoskeleton to provide tension for vesicle fission. Assimilating information from several model systems, we propose a model for PKC-ε mediated vesicle formation for exocytosis during phagocytosis that may be applicable to other processes that require directed membrane delivery and fusion.
Highlights
Our recent papers[1, 2] provide insight into the focal exocytosis that underpins pseudopod extension during Fcγ receptor (FcγR)mediated phagocytosis
We previously demonstrated that PKC-ε concentrates beneath bound targets[16] and that blocking this concentration abolishes FcγR-dependent membrane fusion, significantly reducing phagocytosis[9, 16]
What follows is a theoretical analysis, based on results from many systems, of how PKC-ε could orchestrate the formation of trans Golgi network (TGN)-derived vesicles that translocate to the membrane beneath bound targets, fusing into the forming phagosome to provide membrane for pseudopod extension (Figure 2)
Summary
Our recent papers[1, 2] provide insight into the focal exocytosis that underpins pseudopod extension during Fcγ receptor (FcγR)mediated phagocytosis. As PKC-ε is activated by diacylglycerol (DAG), it was no surprise that translocation to forming phagosomes requires DAG and the (DAG binding) domain of PKC-ε, εC1B8 (Figure 1B). What follows is a theoretical analysis, based on results from many systems, of how PKC-ε could orchestrate the formation of TGN-derived vesicles that translocate to the membrane beneath bound targets, fusing into the forming phagosome to provide membrane for pseudopod extension (Figure 2).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
