Low-density lipoprotein (LDL) is a particle that transports cholesterol throughout the bloodstream. Often called “bad cholesterol,” LDL is essential for various bodily functions. Understanding how LDL enters cells is fundamental to comprehending cellular cholesterol uptake, which ensures cells acquire the cholesterol they need for structural integrity and other biological processes.
What is Low-Density Lipoprotein?
Low-density lipoprotein is one of several types of lipoproteins that transport fat molecules, including cholesterol, within the body’s extracellular fluid. Each LDL particle features a hydrophobic core primarily composed of cholesterol esters, along with some unesterified cholesterol and triglycerides. This core is surrounded by an outer layer made of phospholipids and a single apolipoprotein B-100 molecule (ApoB-100), which helps stabilize the particle.
Their primary function involves delivering cholesterol from the liver to peripheral tissues that require it for cellular processes like membrane synthesis and hormone production. The “low-density” designation stems from their composition, as lipids are less dense than proteins, and LDL contains a relatively high proportion of lipids compared to its protein content.
The LDL Receptor
The LDL receptor (LDLR) is a protein located on the surface of most cells and acts as a specific binding site for LDL particles. This receptor mediates the uptake of cholesterol from the bloodstream into cells. It recognizes the apolipoprotein B-100 molecule embedded in the outer layer of the LDL particle.
The LDLR is an integral membrane glycoprotein that spans the cell membrane. Its structure includes an extracellular binding domain that specifically interacts with ApoB-100 on the LDL particle. The proper functioning of these receptors regulates the amount of LDL cholesterol in the blood.
The Cell’s Entry Mechanism
The entry of LDL into cells is known as receptor-mediated endocytosis. This mechanism begins when LDL particles bind to their specific LDL receptors on the cell surface. These LDL-receptor complexes then gather in specialized regions of the cell membrane called clathrin-coated pits.
These pits are indentations in the cell membrane that are coated on the inside by a protein called clathrin. Once complexes accumulate, these coated pits begin to invaginate, or fold inward, forming a clathrin-coated vesicle that pinches off from the cell surface and moves into the cytoplasm. Immediately after internalization, the clathrin coat disassembles from the vesicle, allowing the uncoated vesicle to fuse with an early endosome. Inside the early endosome, the environment becomes acidic, causing the LDL particle to dissociate, or separate, from its receptor.
Inside the Cell: Processing LDL
After dissociation in the early endosome, the LDL particle and its receptor follow distinct pathways. The LDL receptor is recycled back to the cell surface to bind more LDL particles. This recycling process involves the receptor being sorted into transport vesicles that return it to the plasma membrane, ensuring efficient and continuous uptake of cholesterol.
Meanwhile, the LDL particle, now separated from its receptor, is transported from the endosome to lysosomes. Lysosomes are organelles containing digestive enzymes that break down the LDL particle. The protein component of LDL is degraded into amino acids, and the cholesterol esters are hydrolyzed into free cholesterol and fatty acids. This newly released cholesterol is then utilized by the cell for various functions, such as synthesizing new cell membranes or producing steroid hormones like testosterone and estrogen. The cell maintains its internal cholesterol balance by regulating its own cholesterol synthesis and the number of LDL receptors on its surface.