Article ; Online: The small GTPase RAB10 regulates endosomal recycling of the LDL receptor and transferrin receptor in hepatocytes.
2022 Volume 63, Issue 8, Page(s) 100248
Abstract: The low-density lipoprotein receptor (LDLR) mediates the hepatic uptake of circulating low-density lipoproteins (LDLs), a process that modulates the development of atherosclerotic cardiovascular disease. We recently identified RAB10, encoding a small ... ...
| Abstract | The low-density lipoprotein receptor (LDLR) mediates the hepatic uptake of circulating low-density lipoproteins (LDLs), a process that modulates the development of atherosclerotic cardiovascular disease. We recently identified RAB10, encoding a small GTPase, as a positive regulator of LDL uptake in hepatocellular carcinoma cells (HuH7) in a genome-wide CRISPR screen, though the underlying molecular mechanism for this effect was unknown. We now report that RAB10 regulates hepatocyte LDL uptake by promoting the recycling of endocytosed LDLR from RAB11-positive endosomes to the plasma membrane. We also show that RAB10 similarly promotes the recycling of the transferrin receptor, which binds the transferrin protein that mediates the transport of iron in the blood, albeit from a distinct RAB4-positive compartment. Taken together, our findings suggest a model in which RAB10 regulates LDL and transferrin uptake by promoting both slow and rapid recycling routes for their respective receptor proteins. |
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| MeSH term(s) | Endocytosis ; Endosomes ; Hepatocytes ; Lipoproteins, LDL ; Monomeric GTP-Binding Proteins ; Receptors, LDL ; Receptors, Transferrin ; Transferrin ; rab GTP-Binding Proteins | |||||
| Chemical Substances | Lipoproteins, LDL ; Receptors, LDL ; Receptors, Transferrin ; Transferrin ; Monomeric GTP-Binding Proteins (EC 3.6.5.2) ; rab GTP-Binding Proteins (EC 3.6.5.2) | |||||
| Language | English | |||||
| Publishing date | 2022-06-24 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, N.I.H., Extramural | |||||
| ZDB-ID | 80154-9 | |||||
| ISSN | 1539-7262 ; 0022-2275 | |||||
| ISSN (online) | 1539-7262 | |||||
| ISSN | 0022-2275 | |||||
| DOI | 10.1016/j.jlr.2022.100248 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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