Abstract
Phagocytosis and macropinocytosis, actin-dependent endocytic pathways that mediate the uptake of particles and fluid, respectively, are fundamental routes that enable cells to sample their environment, eliminate pathogens and endogenous cell debris, and contribute to immunoprotection and the maintenance of tissue homeostasis. These processes require a well-organized network of actin cytoskeletal remodeling and membrane transport, which are spatiotemporally regulated by small GTPases. The Rab family of small GTPases, which functions as molecular switches, plays central roles in intracellular membrane trafficking. Although multiple Rab proteins are localized to phagosomes and regulate phagosome maturation, the precise role of each Rab family member in Fcγ receptor (FcγR)-mediated phagocytosis is not fully characterized. Recently, we revealed that Rab35 and Rab20 are important regulators of phagosome formation and maturation, respectively. This review summarizes the functional implication of these Rab GTPases during FcγR-mediated phagocytosis in macrophages. Currently, compared with our knowledge of the regulatory mechanisms of receptor-mediated endocytosis including phagocytosis, the molecular components and signaling cascades of macropinocytosis remain poorly elucidated. Our time-lapse imaging showed that several Rab GTPases are sequentially recruited to the membrane of macropinosomes. Based on our observations, these findings regarding the spatiotemporal localization of Rab GTPases during macropinocytosis are introduced.
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Acknowledgments
The author would like to thank Prof. Nobukazu Araki (Department of Histology and Cell Biology, School of Medicine, Kagawa University) for his mentorship and support. The author also thanks his colleagues and coworkers for their generous assistance. This study was supported by a Grand-in-Aid for Young Scientists (B) #25860142 from the Japan Society for the Promotion of Science. It was also partially funded by Kagawa University Scientific Research Encourages Research Funding 2015.
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Egami, Y. Molecular imaging analysis of Rab GTPases in the regulation of phagocytosis and macropinocytosis. Anat Sci Int 91, 35–42 (2016). https://doi.org/10.1007/s12565-015-0313-y
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DOI: https://doi.org/10.1007/s12565-015-0313-y