Skip to main content
. 2008 Dec 5;10(1):41–43. doi: 10.1038/embor.2008.240

Figure 1.

Figure 1

Role of ubiquitin and arrestin-like adaptor proteins in receptor internalization and transport. Plasma-membrane proteins such as transporters, receptors (for example, the 7TMR shown here) and channels when active or ready to be internalized, are modified at the plasma membrane by kinases and/or ubiquitin ligases. There are many internalization pathways, probably determined by the adaptor proteins—such as arrestin, ART, Dab2, Numb, ARH, CIN85 and epsin—that bind to the cytoplasmic tail of the transmembrane protein. A common pathway uses AP2 adaptor proteins as a link to clathrin-coated vesicles. The internalization of 7TMRs requires an interaction with ubiquitinated arrestin adaptors, which can mediate either clathrin-dependent or clathrin-independent internalization. However, it is clear that ‘receptor' ubiquitination is not always required for internalization and it might be that phosphorylation is also not essential. Numerous weak affinities are a characteristic of these endocytic events, as has been noted in the text for AP2 adaptor interactions. In the case of arrestins, the attached ubiquitin can interact with accessory proteins that have many ubiquitin-interacting motifs (UIMs; shown here in epsin and EPS15) and these could cluster several arrestin-bound receptors. In addition, the CLAP motifs (that bind to clathrin and AP2 adaptors) found in the β-arrestins and in the accessory proteins also tend to cluster and solidify the accumulation of ‘receptor-cargo' into pits. Once receptors are internalized (by any of the pathways shown) and the endocytic machinery has dissociated, the presence or absence of direct receptor ubiquitination determines whether it is sorted to the lysosomes for degradation—by interacting with components of the ESCRT machinery on endosomes—or to the recycling pathway for re-exposure on the plasma membrane. ARH, autosomal recessive hypercholesterolemia protein; ART, arrestin-related trafficking adaptor; CIN85, Cbl interacting protein of 85 kDa; Dab2, Disabled 2 protein; ENTH, epsin amino-terminal homology domain; ESCRT, endosomal sorting complex required for transport; HRS, hepatocyte growth factor-regulated tyrosine kinase substrate; TSG101, protein product of the tumour susceptibility gene 101; VPS, vacuolar protein sorting; 7TMR, seven transmembrane receptors.