Arrestin (red) moves into preexisting coated pits (green) over time.

Cells form clathrin-coated pits to internalize many cell surface receptors, but can these pits form de novo anywhere on the plasma membrane? On page 665, Santini et al. argue that this is not the case, and that there are particular zones of the membrane specialized for coated pit formation and endocytosis. Although the work focuses specifically on the ability of nonvisual arrestins to drive G protein coupled receptor (GPCR) internalization, the findings suggest that cells maintain defined coated pit zones on the membrane—zones that could be thought of as cellular mouths.

Nonvisual arrestins can bind to the coated pit components clathrin and AP-2, raising the possibility that arrestins induce the formation of new coated pits that internalize GPCRs. But, using fluorescently labeled proteins, the authors determined that GPCR-arrestin complexes relocate to preexisting coated pits after GPCR stimulation, rather than forming new coated pits around the receptors. Once the receptors reach the preexisting pits, the pits become more numerous and clustered. Conditions that disrupt the cortical actin membrane skeleton prevent coated pit clustering. Santini and colleagues suggest that an actin-dependent mechanism forms discrete membrane domains called coated pit zones, possibly analogous to membrane rafts, and that receptors are moved into these zones for internalization. ▪