Fig. 5.

A model for the function of clathrin in coated bud formation. An endocytic cycle starts with the recruitment of adapters (red), endocytic accessory proteins (red), and clathrin (blue) to the plasma membrane. The initially flat coated membrane curves because of random thermal fluctuations (A). The clathrin lattice can adjust to the new curvature because both clathrin and adapters are known to exchange readily between their cytosolic and membrane-bound states (18, 19). Clathrin polymerizes in vitro spontaneously into stable 60- to 150-nm closed baskets, which suggests that a highly curved lattice corresponds to the energetically most stable conformation of the polymer. Considering this, the clathrin lattice will stabilize inwardly protruding plasma membrane deformations until the optimal membrane curvature has been reached. Upon vesicle scission the detached vesicle is uncoated because both AP2 and clathrin are losing their affinity for the membrane, which most likely is because of the hydrolysis of PtdIns-4,5-P₂ to PtdIns-4-P by synaptojanin. In clathrin-depleted cells the AP2 membrane domains are also subject to thermal fluctuations (B), but these lack the directionality that is given to this process when clathrin is present.