The Clathrin Adaptor AP-1A Mediates Basolateral Polarity

Clathrin and the epithelial-specific clathrin adaptor AP-1B mediate basolateral trafficking in epithelia. However, several epithelia lack AP-1B, and mice knocked out for AP-1B are viable, suggesting the existence of additional mechanisms that control basolateral polarity. Here, we demonstrate a distinct role of the ubiquitous clathrin adaptor AP-1A in basolateral protein sorting. Knockdown of AP-1A causes missorting of basolateral proteins in MDCK cells, but only after knockdown of AP-1B, suggesting that AP-1B can compensate for lack of AP-1A. AP-1A localizes predominantly to the TGN, and its knockdown promotes spillover of basolateral proteins into common recycling endosomes, the site of function of AP-1B, suggesting complementary roles of both adaptors in basolateral sorting. Yeast two-hybrid assays detect interactions between the basolateral signal of transferrin receptor and the medium subunits of both AP-1A and AP-1B. The basolateral sorting function of AP-1A reported here establishes AP-1 as a major regulator of epithelial polarity. [Display omitted] ► AP-1A sorts cargo proteins from the TGN to the basolateral plasma membrane ► Loss of AP-1A causes cargo proteins to spill over into recycling endosomes ► AP-1B sorting function at recycling endosomes compensates for AP-1A knockdown ► Transferrin receptor basolateral signal binds noncanonical sites in AP-1A and AP-1B Gravotta et al. find that the ubiquitous clathrin adaptor AP-1A sorts cargo proteins from the trans-Golgi network to the basolateral membrane. AP-1A knockdown reroutes cargo into recycling endosomes for compensatory sorting by the epithelial-specific adaptor AP-1B. AP-1A and AP-1B are thus partially redundant, mediating basolateral sorting via distinct routes.