Regular Research Articles
The small GTPase RAB10 regulates endosomal recycling of the LDL receptor and transferrin receptor in hepatocytesThe 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.
Generation and validation of a conditional knockout mouse model for desmosterolosisThe enzyme 3β-hydroxysterol-Δ24 reductase (DHCR24, EC 18.104.22.168) catalyzes the conversion of desmosterol to cholesterol and is obligatory for post-squalene cholesterol synthesis. Genetic loss of this enzyme results in desmosterolosis (MIM # 602398 ), a rare disease that presents with multiple congenital anomalies, features of which overlap with subjects with the Smith-Lemli-Opitz syndrome (another post-squalene cholesterol disorder). Global knockout (KO) of Dhcr24 in mice recapitulates the biochemical phenotype, but pups die within 24 h from a lethal dermopathy, limiting its utility as a disease model.