Figure 2.

Signals and adaptor proteins involved in polarized sorting. (A) Sequences of the cytosolic tails of the indicated proteins, with critical residues of polarized sorting signals highlighted in red. Signals are categorized as YXXØ, [DE]XXXL[LI], or noncanonical. The transmembrane domain (TM) and the number of additional residues in each tail are indicated. For the TfR, the basolateral sorting signal is GDNS, but the somatodendritic sorting signal is YTRF. The LDLR has a proximal signal with one tyrosine residue and an acidic cluster (EDE) and a distal signal with two tyrosine residues and another acidic cluster (EED). (B) Adaptor proteins that have been implicated in polarized sorting. AP-1 and AP-4 are composed of four homologous subunits, as reflected by the color scheme. The core, hinge, and ear domains of the AP complexes and the PTB domain of ARH and Numb are indicated. Folded regions are represented by geometric shapes and disordered regions by wavy lines. The AP-2, AP-3, AP-5, and COPI-F complexes are homologous to AP-1 and AP-4, but to date they have not been directly implicated in polarized sorting. Three of the AP-1 subunits occur as isoforms encoded by different genes: γ1 and γ2; μ1A and μ1B; and σ1A, σ1B, and σ1C. PM, plasma membrane. (C) Schematic representation of a clathrin-coated bud on the TGN/RE containing AP-1, Numb, and ARH as adaptor proteins. Arf proteins recruit AP-1 to membranes and promote its conformational activation. Clathrin triskelia polymerize onto the adaptor proteins to form a polyhedral coat. Cargos are gathered into the coated buds by interaction of sorting signals with the adaptor proteins.