5.13
受体介导的内吞作用
受体介导的内吞作用是将大量的特异性分子与细胞表面受体结合后导入细胞的过程。与这些受体结合的分子通过细胞膜向内折叠进入细胞，细胞膜最终被挤压成细胞内的小泡。结构蛋白，如网格蛋白，包裹着出芽囊泡，使其呈圆形。
氯氰菊酯介导的低密度脂蛋白内吞
受体介导的内吞作用的一个典型例子是低密度脂蛋白（LDL胆固醇）进入…
Receptor-mediated endocytosis is a specialized form of pinocytosis where cell surface receptors mediate the active uptake of specific molecules such as low-density lipoproteins, otherwise known as LDL, the bad cholesterol.
To initiate the process, adapter proteins interact with specific lipids, phosphatidylinositol phosphates or PIPs in the membrane, to induce a conformational change in the subunits that expose the binding sites for cell surface cargo receptors. When a signal molecule, like LDL, binds to a receptor such as the Apo-B protein here, it causes the membrane to curve inwards, allowing for additional binding in the same vicinity of the growing pit. More protein structures, clathrin triskelions, attach and form the clathrin-coated pit with the cargo facing inside.
Other membrane bending and fusion proteins are recruited to the neck and pinch off the clathrin-coated vesicle. The coating is rapidly released and the naked vesicle will often fuse with endosomes to be further processed by the cell. The cargo receptors disassociate from the LDL in the lower-pH environment within the endosome and intact receptors will be shuttled back to the membrane ready to bind other signaling molecules. The LDL will be further processed and broken down into cholesterol and amino acids.
Q1: What role do adapter proteins play in receptor-mediated endocytosis?
Adapter proteins interact with phosphatidylinositol phosphates (PIPs) in the cell membrane to induce conformational changes that expose binding sites for cargo receptors. These proteins facilitate the attachment of clathrin triskelions to the membrane's inner surface, initiating the formation of the clathrin-coated pit and enabling the membrane to curve inward for vesicle formation.
Q2: How does the pH environment inside an endosome affect LDL and its receptor?
The lower pH inside the endosome causes LDL to dissociate from its receptor protein, the Apo-B receptor. This pH-dependent separation allows intact receptors to be recycled back to the cell membrane for reuse, while LDL remains in the endosome for further processing and breakdown into cholesterol and amino acids.
Q3: What is the function of clathrin triskelions in forming endocytic vesicles?
Clathrin triskelions are protein structures that attach to the inner membrane surface and polymerize to form the clathrin-coated pit. These proteins create a lattice-like coating that gives the budding vesicle its characteristic round shape and helps stabilize the inward membrane curvature necessary for vesicle formation and cargo internalization.
Q4: How do pathogens exploit receptor-mediated endocytosis to invade host cells?
Pathogens like influenza virus and Bacillus anthracis hijack host cell receptors by binding to them on the cell surface. The virus or toxin is then internalized through the cell's native endocytic pathways. Once inside, some pathogens escape the endosome to cause infection, while others release toxins that trigger cellular damage.
Q5: What is the difference between clathrin-mediated and caveolin-mediated endocytosis?
Clathrin-mediated endocytosis involves clathrin proteins binding to the outer membrane surface, while caveolin-mediated endocytosis involves caveolin proteins inserting directly into the lipid bilayer. Despite this structural difference, both pathways result in membrane curvature and vesicle formation, though they may internalize different cargo molecules.
Q6: How is iron transported into cells through receptor-mediated endocytosis?
Iron enters cells via endocytosis of transferrin, an iron-binding protein that binds to the transferrin receptor (TfR) on the cell surface. A clathrin-coated vesicle forms and transports transferrin into the cell. In the early endosome, decreased pH releases iron from transferrin, while the receptor and empty transferrin are recycled back to the cell surface.
Q7: How does receptor-mediated endocytosis regulate cell signaling?
Receptor-mediated endocytosis regulates signaling through sequestration, where signal receptors are internalized and stored in vesicles until needed or degraded by proteolytic enzymes. Additionally, some signaling pathways require endocytosis itself to allow signal transduction to occur, making the process essential for controlling cellular communication and response.