期刊
JOURNAL OF LIPID RESEARCH
卷 63, 期 8, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.jlr.2022.100248
关键词
low density lipoprotein receptor; receptors; protein trafficking; cholesterol; lipoproteins; CRISPR screen; HuH7 cells; endocytosis; RAB10; RAB11
资金
- National Institutes of Health [R35-HL135793T, K08-HL148552]
RAB10 regulates the uptake of LDL and transferrin in hepatocytes by promoting the recycling of their respective receptors from specific compartments.
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 carci-noma cells (HuH7) in a genome-wide CRISPR screen, though the underlying molecular mecha-nism 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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