FIGURE 14-31 The transferrin cycle operates in all growing mammalian cells. Step 1: The transferrin dimer carrying two bound atoms of Fe³⁺, called ferrotransferrin, binds to the transferrin receptor at the cell surface. Step 2: Interaction between the tail of the transferrin receptor and the AP2 adapter complex incorporates the receptor-ligand complex into endocytic clathrin-coated vesicles. Steps 3 and 4: The vesicle coat is shed, and the endocytic vesicles fuse with the membrane of the endosome. Fe³⁺ is released from the receptor-ferrotransferrin complex in the acidic late endosome compartment. Step 5: The apotransferrin protein remains bound to its receptor at this pH, and they are recycled to the cell surface together. Step 6: The neutral pH of the exterior medium causes release of the iron-free apotransferrin. See A. Ciechanover et al., 1983, J. Biol. Chem. 258:9681.