The Adaptor Protein-1 μ1B Subunit Expands the Repertoire of Basolateral Sorting Signal Recognition in Epithelial Cells

An outstanding question in protein sorting is why polarized epithelial cells express two isoforms of the mu 1 subunit of the AP-1 clathrin adaptor complex: the ubiquitous mu 1A and the epithelial-specific mu 1B. Previous studies led to the notion that mu 1A and mu 1B mediate basolateral sorting predominantly from the trans-Golgi network (TGN) and recycling endosomes, respectively. Using improved analytical tools, however, we find that mu 1A and mu 1B largely colocalize with each other. They also colocalize to similar extents with TGN and recycling endosome markers, as well as with basolateral cargoes transiting biosynthetic and endocytic-recycling routes. Instead, the two isoforms differ in their signal-recognition specificity. In particular, mu 1B preferentially binds a subset of signals from cargoes that are sorted basolaterally in a mu 1B-dependent manner. We conclude that expression of distinct mu 1 isoforms in epithelial cells expands the repertoire of signals recognized by AP-1 for sorting of a broader range of cargoes to the basolateral surface.