Since clathrin itself cannot bind to membranes, it requires the help of adapter proteins. For this purpose, the terminal domain, which mediates the binding to these proteins, extends far into the centre of a clathrin cage (Figure 1-3 B). In contrast, the light chains are located on the outside (Figure 1-3 C) of a cage, which makes them easily accessible for regulatory proteins.
These clathrin cages have diameters ranging from 50 to 100 nm and are covered by a scaffold of mostly 12 penta- and 8 hexagons of a total of 36 triple skeletons of clathrin. This fibrous protein consists of a heavy chain (180,000 daltons [Da]) and a light chain (35,000 to 40,000 Da). In addition, the 900 amino acid dynamin, which can bind and hydrolyze GTP, is also found in the vesicle coat. Clathrin does not itself bind to membranes, but via different adaptor protein complexes (AP complexes). These AP complexes dock to the heavy chains of clathrin. In addition, the AP complexes bind to membrane lipids and membrane proteins and thus mediate the binding of clathrin to membranes. AP-2 mediates the formation of "clathrin-coated vesicles" (CCV) at the plasma membrane. AP-1 mediates CCV formation at the trans-Golgi network, the last compartment of the protein synthesis apparatus in the secretory transport pathway. AP4 is the only representative of the heterotetrameric adaptor complexes and does not have a typical clathrin box sequence. Therefore, the involvement of AP4 in the formation of CCVs is controversial. The clathrin envelope is rapidly lost within the cell. An endosome is formed which fuses with membrane vesicles from the Golgi apparatus and forms larger edosomal compartments. Receptors are separated from the ligands and transported back to the cell surface in membrane vesicles (receptor recycling). The ligands enter a multivesicular body (endolysosome). Hydrolases are transported from the Golgi apparatus in clathrin-enveloped vesicles to the endolysosome.