AP-1A (green) and AP-1B (red) do not colocalize, despite similarities.

In polarized epithelial cells, the clathrin adaptor complex AP-1B targets many proteins to the basolateral membrane, but how does AP-1B separate its cargos away from the ubiquitous AP-1A complex, from which it differs only slightly? A pair of papers in this issue identify several unique components of the AP-1B targeting system, and show that AP-1B segregates into a distinct membrane domain that may connect two basolateral sorting pathways.

Folsch et al. (page 351) show that, despite their strong homology, AP-1A and AP-1B complexes segregate onto distinct populations of clathrin-coated membranes in MDCK cells. In the Golgi apparatus, AP-1B specifically recruits components of the exocyst complex, which is thought to target transport vesicles to the basolateral plasma membrane. AP-1B also localizes to perinuclear regions that appear to be in a post-Golgi compartment that is distinct from the trans-Golgi network but very close to transferrin-positive recycling endosomes.

The post-Golgi localization of AP-1B is especially intriguing, as polarized cells must sort both internalized receptors in the endosome recycling pathway and newly synthesized proteins from the Golgi apparatus. The two sorting pathways may intersect in the perinuclear region.

Although many basolateral proteins rely on AP-1B for targeting, not all do—a fact underscored by Ang et al. on page 339. These authors show that disrupting the function of either Rab8 or Cdc42 specifically blocks AP-1B–mediated transport, leaving AP-1B–independent basolateral proteins unaffected. Rab8, a mammalian homologue of yeast Sec4p, appears in the same perinuclear region where AP-1B, exocyst components, and recycling endosomes appear to congregate. The authors are now using an immobilized Golgi apparatus assay to identify additional components of the sorting system. ▪