The small GTPase RAB10 regulates endosomal recycling of the LDL receptor and transferrin receptor in hepatocytes.
J Lipid Res
; 63(8): 100248, 2022 08.
Article
em En
| MEDLINE
| ID: mdl-35753407
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Monoméricas de Ligação ao GTP
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
J Lipid Res
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos