18.4
Receptor-mediated Endocytosis
Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecul…
Receptor-mediated endocytosis is a form of endocytosis where molecules, including metabolites, hormones, and nutrients, are internalized through their specific cell-surface receptors.
Once a molecule binds to its specific receptor on the cell membrane, the membrane bends inwards. Then, clathrin triskelions, structural proteins, bind to adaptor proteins and polymerize to form a clathrin-coated pit.
Other membrane-bending and fusion proteins are recruited to the neck of the clathrin-coated pit and pinch it off. The coating is rapidly released and the naked vesicle fuses with an early endosome.
The early endosome has two domains—tubular and vacuolar, with different internal pHs. The low pH of the vacuolar domain causes the endocytosed ligand to be released from its receptor.
While the ligand is retained in the vacuolar domain and is later processed, the associated receptor remains in the tubular domain due to the large surface area to volume ratio of the tubules. The receptor is then transported back to the cell membrane.
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Q1: What is receptor-mediated endocytosis and how does it work?
Receptor-mediated endocytosis is a process where specific molecules bind to cell-surface receptors, triggering the membrane to fold inward and form a vesicle. Clathrin proteins coat the budding vesicle, and accessory proteins pinch off the neck to release it into the cell. The vesicle then fuses with the early endosome for further processing.
Q2: What role does clathrin play in receptor-mediated endocytosis?
Clathrin is a structural protein that binds to adaptor proteins on the inner membrane surface. It polymerizes to form a clathrin-coated pit that bends the membrane inward. The clathrin coat is rapidly released once the vesicle forms, exposing a naked vesicle ready to fuse with the early endosome.
Q3: How does the early endosome separate ligands from their receptors?
The early endosome contains two domains with different internal pH levels. The low pH in the vacuolar domain causes endocytosed ligands to dissociate from their receptors. Receptors remain in the tubular domain due to its large surface area and are recycled back to the cell membrane.
Q4: What happens to LDL cholesterol after receptor-mediated endocytosis?
LDL binds to receptors and enters the cell via clathrin-coated vesicles. In the early endosome, LDL dissociates from receptors due to low pH. The LDL remains in the endosome, which later fuses with a lysosome where digestive enzymes break it down into free cholesterol for cellular use.
Q5: How does receptor-mediated endocytosis regulate cell signaling?
Receptor-mediated endocytosis regulates signaling through sequestration, bringing receptors inside the cell to control signal intensity. Some receptors are stored in vesicles until needed, while others are degraded by proteolytic enzymes. Additionally, some signaling pathways require endocytosis to allow signal transduction into the cell.
Q6: How do pathogens exploit receptor-mediated endocytosis to invade cells?
Bacteria and viruses hijack host cell receptors to gain entry. The influenza virus binds to cell-surface receptors and uses clathrin-mediated endocytosis to enter. Bacillus anthracis produces anthrax toxin that binds to host receptors, undergoes endocytosis, and escapes the endosome to cause cellular damage.
Q7: What is the difference between clathrin and caveolin in endocytosis?
Clathrin binds to the outer surface of the cell membrane and forms coated pits that bud inward. Caveolin, an alternative endocytic pathway, inserts itself directly into the lipid bilayer rather than coating the membrane surface. Both pathways internalize molecules, but they differ in their structural mechanisms and membrane interactions.