2.5 The endocytic pathways and lysosomes
Endocytosis is the process by which cells internalise molecules from the outside, and it includes pinocytosis, the uptake of small soluble molecules in vesicles, and phagocytosis, the internalisation of large insoluble particles. These are two ends of a spectrum as seen microscopically, but the receptors, the subsequent intracellular trafficking pathways and the fate of the internalised molecules, vary depending on the cell type and its functions. The endocytic pathway comprises two distinct kinds of endosome, early endosomes and late endosomes. Material taken up by endocytosis passes from the early endosomes to the late endosomes and from there may intersect with trafficking pathways from the Golgi apparatus, or may be directed to lysosomes or to the Golgi. The exact pathway depends on the cell and the material that has been internalised.
It is important to distinguish receptor-mediated endocytosis from the general non-specific endocytic uptake of material from the medium. For example, transferrin (the iron transport molecule present in blood plasma) is taken up after binding to a transferrin receptor, which is expressed on a variety of cells. The receptor with its bound transferrin is internalised by budding of vesicles from the plasma membrane, and these fuse with endosomes. In the acidic environment of the endosome, iron dissociates from transferrin to give apotransferrin, which is then recycled back to the plasma membrane to collect more iron (Figure 12). The receptor is similarly recycled.
A different pathway is taken by receptors such as the EGF (epidermal growth factor) receptor, which together with its ligand moves from an early endosomal compartment to a late endosome and from there to lysosomes for degradation (Figure 12). This is a mechanism for reducing the number of receptors on the cell surface, a process that is controlled, in many cases, by the phosphorylation of the receptors.
Notice that the transferrin receptor can be used many times to take up iron, whereas the EGF receptor has a single function – signalling cell division. Once the cell has received the appropriate signal then the EGF receptor is no longer required (at least for a while) and, by degrading the receptor, the cell becomes less sensitive to further signals.