SorLAs trafficking in polarized (A) compared to non-polarized (B) cells. In polarized cells, SorLA is secreted to the basolateral plasma membrane (1), a transport that may go through common recycling endosomes. The initial polarized transport is independent of the acidic cluster. Afterwards, SorLA is internalized, either to basolateral sorting endosomes (2a) and the common endosomal system, or sent via specialized transcytotic endosomes to the apical membrane (2b), as indicated by the relatively low polarity index. From the apical membrane, proteins are internalized via EEA1-positive apical early endosomes to apical sorting endosomes (3). In non-polarized cells, SorLA is either secreted (4) and afterwards internalized to the endosomal system (5) and returned to the TGN for recycling (6) or sent directly from the TGN to the endosomal system (7). Approximately 10% is localized at the plasma membrane at steady-state. * indicates a step where AP1 is believed to be involved, while ^ indicates a step possibly involving Vps35.
Abbreviations: AEE (apical early endosomes), EE (early endosomes), LE (late endosomes), TGN (trans Golgi network), BSE (basolateral sorting endosomes), ASE (apical sorting endosomes), L (lysosomes).