Sorting it out: AP-2 and alternate clathrin adaptors in endocytic cargo selection

Abstract

The AP-2 adaptor complex is widely viewed as a linchpin molecule in clathrin-mediated endocytosis, simultaneously binding both clathrin and receptors. This dual interaction couples cargo capture with clathrin coat assembly, but it has now been discovered that the association with cargo is tightly regulated. Remarkably, AP-2 is not obligatory for all clathrin-mediated uptake, and several alternate adaptors appear to perform similar sorting and assembly functions at the clathrin bud site.

Figure 1.

The endocytic adaptor interaction web. A schematic representation of the protein–protein interactions possible between clathrin, AP-2, and alternate endocytic adaptors. The sorting signal or putative cargo types recognized by the different adaptors are boxed in black. PtdIns(4,5)P₂-binding sites are indicated by the spherical gray attachments. AP-2 is modeled on the known molecular architecture of the core and appendages, but the different proteins are not to scale. pGPCR, phosphorylated G protein–coupled receptor; AMPA-R, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor.