Protein Targeting and Degradation:- Cells Import Proteins by Receptor-Mediated Endocytosis
Some proteins are imported into cells from the sur rounding medium; examples in eukaryotes include low density lipoprotein (LDL), the iron-carrying protein transferrin, peptide hormones, and circulating proteins destined for degradation. The proteins bind to receptors in invaginations of the membrane called coated pits, which concentrate endocytic receptors in preference to other cell-surface proteins. The pits are coated on their cytosolic side with a lattice of the protein clathrin, which forms closed polyhedral structures (Fig. 1). The clathrin lattice grows as more receptors are occupied by target proteins, until a complete membrane-bounded endocytic vesicle buds off the plasma membrane and enters the cytoplasm. The clathrin is quickly removed by uncoating enzymes, and the vesicle fuses with an endosome. ATPase activity in the endosomal membranes reduces the pH therein, facilitating dissociation of receptors from their target proteins.
The imported proteins and receptors then go their separate ways, their fates varying with the cell and protein type. Transferrin and its receptor are eventually re cycled. Some hormones, growth factors, and immune complexes, after eliciting the appropriate cellular response, are degraded along with their receptors. LDL is degraded after the associated cholesterol has been de livered to its destination, but the LDL receptor is recycled . Receptor-mediated endocytosis is exploited by some toxins and viruses to gain entry to cells. Influenza virus , diphtheria toxin, and cholera toxin all enter cells in this way.
FIGURE 1 Clathrin. (a) Three light (L) chains (Mr 35,000) and three heavy (H) chains (Mr 180,000) of the (HL)3 clathrin unit, or ganized as a three-legged structure called a triskelion. (b) Triskelion tend to assemble into polyhedral lattices. (c) Electron micrograph of a coated pit on the cytosolic face of the plasma membrane of a fibroblast.
