Investigating how bad cholesterol is removed from the body

The molecular basis of the decreased clathrin-mediated endocytosis of LDL in quiescent hepatocytes

When the levels of LDL (‘bad cholesterol’) are raised in the blood, our chances of developing coronary heart disease increase. Statin drugs lower cholesterol in the body by blocking its production in the liver. However, in response to this decrease in cholesterol production the body also decreases its ‘bad cholesterol’ uptake into liver cells (the usual way LDL is removed from the body). LDL is taken up into liver cells by a process called clathrin-mediated endocytosis. Here receptors on the outer membrane of the cell bind LDL and then absorb it into the cell by budding inwards forming a package coated with a protein called clathrin. Dr Emmanuel Boucrot and colleagues at University College London noted that the rate at which liver cells perform clathrin mediated endocytosis depends on the activity state of the liver cell, and that a protein, FCHo2, is chemically changed when the cells are in the resting (quiescent) phase. They suggest that chemical changes in FCHo2 influence LDL uptake by liver cells. Dr Boucrot has now been awarded a BHF PhD studentship to train a student to investigate how FCHo2 regulates clathrin mediated endocytosis and how uptake of LDL into liver cells is down regulated in liver cells in the resting state. Understanding these processes, could create opportunities to design new strategies to increase LDL uptake in the liver and thus up-regulate its clearance from the body.