Quantitative studies of the distribution of EGF receptors in coated and uncoated regions of the plasma membrane are difficult because the presence of receptors in coated pits is transient and its amount is very low. Pathways of internalization and intracellular sorting of GF receptors. Clathrin, AP-2 and eps15 are indicated as components of the clathrin coat. The coats involved in the second pathway are not known. Both clathrin-dependent and independent internalization pathways lead receptors to the early endosomal compartments.
Black arrows show recycling of occupied and unoccupied receptors from endosomes.
The relative width of arrows indicates that the recycling is much slow from intermediate and late endosomes than from the early compartment. Conformational rearrangements of the clathrin lattice result in deep invagination of the coated pit and fission of the coated endocytic vesicle containing cargo proteins. Several stages of the coated pit cycle require energy, physiological temperature, and are regulated by dynamin and other GTP-binding proteins. Although the possibility exists that clathrin has dissociated during fixation and other sample preparation procedures, it has been proposed that EGF receptors can be internalized by clathrin-independent pathway in some cells. Although endocytosis of some receptors can occur in the absence of functional coated pits, clathrin-dependent endocytosis is the most efficient and fastest pathway.