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Rab10-Positive Tubular Structures Represent a Novel Endocytic Pathway That Diverges From Canonical Macropinocytosis in RAW264 Macrophages
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Abstract
Using the optogenetic photo-manipulation of photoactivatable (PA)-Rac1, remarkable cell surface ruffling and the formation of a macropinocytic cup (premacropinosome) could be induced in the region of RAW264 macrophages irradiated with blue light due to the activation of PA-Rac1. However, the completion of macropinosome formation did not occur until Rac1 was deactivated by the removal of the light stimulus. Following PA-Rac1 deactivation, some premacropinosomes closed into intracellular macropinosomes, whereas many others transformed into long Rab10-positive tubules without forming typical macropinosomes. These Rab10-positive tubules moved centripetally towards the perinuclear Golgi region along microtubules. Surprisingly, these Rab10-positive tubules did not contain any endosome/lysosome compartment markers, such as Rab5, Rab7, or LAMP1, suggesting that the Rab10-positive tubules were not part of the degradation pathway for lysosomes. These Rab10-positive tubules were distinct from recycling endosomal compartments, which are labeled with Rab4, Rab11, or SNX1. These findings suggested that these Rab10-positive tubules may be a part of non-degradative endocytic pathway that has never been known. The formation of Rab10-positive tubules from premacropinosomes was also observed in control and phorbol myristate acetate (PMA)-stimulated macrophages, although their frequencies were low. Interestingly, the formation of Rab10-positive premacropinosomes and tubules was not inhibited by phosphoinositide 3-kinase (PI3K) inhibitors, while the classical macropinosome formation requires PI3K activity. Thus, this study provides evidence to support the existence of Rab10-positive tubules as a novel endocytic pathway that diverges from canonical macropinocytosis.
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RAB10 has been implicated in diverse areas of membrane trafficking in different cell types, including formation of noncanonical macropinosome tubules in macrophages, vesicle transportation from early endosome to recycling endosome in C. elegans, and Golgi to plasma membrane transport in macrophages.
“RAB10 has also been implicated in diverse areas of membrane trafficking in different cell types, including formation of noncanonical macropinosome tubules in macrophages (49), vesicle transportation from early endosome to recycling endosome in C. elegans (31), and Golgi to plasma membrane transport in macrophages (32).”
From The small GTPase RAB10 regulates endosomal recycling of the LDL receptor and transferrin receptor in hepatocytes (2022) · cites this paper as [49]
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Araki, N., Johnson, M. T., & Swanson, J. A. (1996) · The Journal of cell biology · doi:10.1083/jcb.135.5.1249 · Cited by 949 · cited 13×
“Although Rab10 accumulation on the Akt-PH-positive macropinosomal membrane was not seen in RAW cells during PA-Rac1 ON-OFF cycling, Rab10-positive premacropinosomes without Akt-PH signals were frequently observed after treatment with PI3K inhibitors (Figures 8A, B Supplementary Movies 16, 17).”
BackgroundInfluentialSelf-citationFujii, M., Kawai, K., Egami, Y., & Araki, N. (2013) · Scientific Reports · doi:10.1038/srep02385 · Cited by 137
Self-citationLRRK2 and Rab10 coordinate macropinocytosis to mediate immunological responses in phagocytes
Liu, Z., Xu, E., Zhao, H. T., Cole, T., & West, A. B. (2020) · The EMBO Journal · doi:10.15252/embj.2020104862 · Cited by 90
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Cited by
Sorted by citations
Khan, T. G., Ginsburg, D., & Emmer, B. T. (2022) · Journal of Lipid Research · doi:10.1016/j.jlr.2022.100248 · Cited by 21
Potential Roles of SNX17, Rab11, and Rab5 in LDLR Recycling
Zhao, X., Long, S., Zhu, M., Hao, H., Liao, Y., Zhang, C., & Liu, Z. (2025) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.125.322498 · Cited by 8
Metadata
- Authors
- Kawai, K., Nishigaki, A., Moriya, S., Egami, Y., & Araki, N.
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2021-05-31
- Volume
- 12
- ISSN
- 1664-3224
- PMC
- PMC8203412
- Cited by
- 9
- References
- 3
- Funders
- Japan Society for the Promotion of Science
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