Desoribe endocytosis of LDL by the cell
Low-Density Lipoprotein (LDL) is the primary transporter of cholesterol in the bloodstream. Cells acquire cholesterol from LDL particles through a highly specific process called receptor-mediated endocytosis, which is a classic example of clathrin-dependent endocytosis.
This process begins when LDL particles bind to LDL receptors (LDLR) located on the plasma membrane. These receptors are transmembrane glycoproteins that specifically recognize apolipoprotein B-100 (ApoB-100) on the surface of LDL. The receptor-ligand complexes cluster in membrane regions called clathrin-coated pits. These regions are lined by the protein clathrin, which forms a polygonal lattice that shapes the invaginated membrane into a vesicle.
As the clathrin-coated pit deepens, the membrane undergoes scission with the help of dynamin, a GTPase that pinches off the vesicle from the plasma membrane. This forms a clathrin-coated vesicle containing the LDL-receptor complexes. The clathrin coat is then rapidly removed and the uncoated vesicle fuses with an early endosome.
Inside the early endosome, the acidic pH (around 5.0–6.0) causes LDL particles to dissociate from their receptors. The LDL receptors are recycled back to the plasma membrane via recycling endosomes, ready to mediate further rounds of uptake. The LDL particles are then transferred to late endosomes and lysosomes, where they are degraded by hydrolytic enzymes.
In the lysosome, the cholesteryl esters within LDL are hydrolyzed to release free cholesterol, which is utilized by the cell for membrane synthesis, steroid hormone production, or stored as cholesteryl esters by the enzyme ACAT (acyl-CoA cholesterol acyltransferase).
This mechanism is essential for cholesterol homeostasis. A defect in the LDL receptor or associated proteins (e.g., in familial hypercholesterolemia) leads to decreased LDL clearance and elevated plasma cholesterol levels, increasing the risk of atherosclerosis and cardiovascular disease.
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