Figure 9.

A scheme for clathrin-coated pit assembly at the plasma membrane. Docking sites for AP2 at the plasma membrane become exposed or activated (step 1), resulting in the recruitment of AP2 molecules from the cytosol (step 2). Once bound to the docking site, the clathrin-binding activity of the AP2 is expressed, clathrin trimers are recruited, and lattice assembly begins (step 3), perhaps promoted by AP2 self-association (dotted lines [Beck and Keen, 1991]). Transmembrane receptors then become associated with the growing or completed coat via internalization motifs in their cytoplasmic domains (step 4). For receptors with tyrosine-based signals, this association likely occurs through interaction with the μ₂ subunit of the AP2 complex; interaction sites within the coat for receptors with di-leucine and acidic cluster/casein kinase II substrate signals are not certain. For some G protein-coupled receptors, arrestins mediate binding of the receptor to the terminal domains of the clathrin triskelia (Goodman et al., 1996, 1997).