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RAB-10 Is Required for Endocytic Recycling in the Caenorhabditis elegans Intestine
Abstract
The endocytic pathway of eukaryotes is essential for the internalization and trafficking of macromolecules, fluid, membranes, and membrane proteins. One of the most enigmatic aspects of this process is endocytic recycling, the return of macromolecules (often receptors) and fluid from endosomes to the plasma membrane. We have previously shown that the EH-domain protein RME-1 is a critical regulator of endocytic recycling in worms and mammals. Here we identify the RAB-10 protein as a key regulator of endocytic recycling upstream of RME-1 in polarized epithelial cells of the Caenorhabditis elegans intestine. rab-10 null mutant intestinal cells accumulate abnormally abundant RAB-5-positive early endosomes, some of which are enlarged by more than 10-fold. Conversely most RME-1-positive recycling endosomes are lost in rab-10 mutants. The abnormal early endosomes in rab-10 mutants accumulate basolaterally recycling transmembrane cargo molecules and basolaterally recycling fluid, consistent with a block in basolateral transport. These results indicate a role for RAB-10 in basolateral recycling upstream of RME-1. We found that a functional GFP-RAB-10 reporter protein is localized to endosomes and Golgi in wild-type intestinal cells consistent with a direct role for RAB-10 in this transport pathway.
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RAB10 has been localized to multiple subcellular compartments in different cell types including the endoplasmic reticulum, trans Golgi network, early endosomes, recycling endosomes, phagosomes, and primary cilia.
“Consistent with this wide range of functions, RAB10 has been localized to multiple subcellular compartments in different cell types including the endoplasmic reticulum, trans Golgi network, early endosomes, recycling endosomes, phagosomes, and primary cilia (25, 31, 32, 50, 51, 52).”
From The small GTPase RAB10 regulates endosomal recycling of the LDL receptor and transferrin receptor in hepatocytes (2022) · cites this paper as [31]
The Results (page unavailable) place RAB-10 on a subset of early endosomes and describe its association with the TGN and/or apical recycling endosomes in C. elegans intestinal cells. The paper does not establish the claimed localization to the endoplasmic reticulum, phagosomes, or primary cilia. (LLM, conf=0.88)
Experimental — accuracy not yet measuredRab10 is involved in recycling and present at the trans-Golgi network (TGN).
“In addition, previously it has been shown that Rab10 is involved recycling and present at the trans-Golgi network (TGN) [12, 72].”
From Cellular and subcellular localization of Rab10 and phospho-T73 Rab10 in the mouse and human brain (2023) · cites this paper as [12]
The Results (page unavailable) support a role for RAB-10 in recycling in the C. elegans intestine. They describe TGN localization more cautiously: RAB-10-labeled structures are “probably TGN,” with significant residence on “TGN and/or apical recycling endosomes.” The claim presents TGN localization as definite. (LLM, conf=0.86)
Experimental — accuracy not yet measuredRAB10 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 [31]
Activation of RAB10 is heavily implicated in general endosomal cargo recycling.
“Activation of RAB10 is heavily implicated in general endosomal cargo recycling85–93”
From Mapping of endosomal proximity proteomes reveals Retromer as a hub for RAB GTPase regulation (2025) · cites this paper as [85]
The study extended the known Retromer regulators to include DENND4A and DENND4C, TBC1D13, and a TBC1D1/TBC1D4 heterodimer, establishing mechanistic links between Retromer and the switching of RAB10 and RAB35.
“We have now extended these regulators to include DENND4A and DENND4C, TBC1D13, and a TBC1D1/TBC1D4 heterodimer, and in so doing, established mechanistic links between Retromer and the switching of RAB10 and RAB35; two RAB GTPases previously linked to the regulation of endosomal cargo recycling85,88–90,92,96,101,121,122.”
From Mapping of endosomal proximity proteomes reveals Retromer as a hub for RAB GTPase regulation (2025) · cites this paper as [85]
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Metadata
- Authors
- Chen, C. C.-H., Schweinsberg, P. J., Vashist, S., Mareiniss, D. P., Lambie, E. J., & Grant, B. D.
- Affiliations
- Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854
- Department of Biological Sciences, Dartmouth College, Hanover, NH 03755
- Venue
- Molecular Biology of the Cell
- Published
- 2006-03
- Volume
- 17
- Issue
- 3
- Pages
- 1286-1297
- ISSN
- 1059-1524
- 1939-4586
- Cited by
- 202
- References
- 0
- Language
- en
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