Taking the scenic route: biosynthetic traffic to the plasma membrane in polarized epithelial cells

Abstract

The maintenance of epithelial cell function requires the establishment and continuous renewal of differentiated apical and basolateral plasma membrane domains with distinct lipid and protein compositions. Newly synthesized proteins destined for either surface domain are processed along the biosynthetic pathway and segregated into distinct subsets of transport carriers emanating from the trans-Golgi network. Recent studies have illuminated additional complexities in the subsequent delivery of these proteins to the cell surface. In particular, multiple routes to the apical and basolateral cell surfaces have been uncovered, and many of these involve indirect passage through endocytic compartments. This review summarizes our current understanding of these routes and discusses open issues that remain to be clarified.

Figure 1. Distribution of recycling endosomes in polarized MDCK cells

Filter-grown MDCK cells stably expressing GFP-Rab11 (green) were incubated with basolaterally added canine Tf for 30 min, then fixed and processed for indirect immunofluorescence with antibodies against canine Tf (in red) and the tight junction marker ZO-1 (in blue). Individual and merged confocal sections taken just beneath the apical surface and at the level of the tight junction/lateral border are shown. An xz section is shown in the bottom panel. Note the segregation of Rab11 and transferrin, which mark the apical recycling and common recycling endosomes, respectively.

Figure 2. Biosynthetic trafficking routes in polarized kidney cells

The model depicts the multiple pathways used by biosynthetic cargo proteins to reach their final destinations from the TGN. Arrows indicate the paths from one organelle to the next. Specific cargo proteins that are thought to utilize each route are noted on the right. Direct routes to the apical and basolateral surface as well as a pathway via the basolateral early endosomes (BEE; pathways 1 and 2) are predicted but have not been experimentally verified. AEE, apical early endosome; ARE, apical recycling endosome; CRE, common recycling endosome. Trafficking pathways to the primary cilium are not well defined and are omitted in this model, as are the trafficking routes used by proteins not destined for the plasma membrane. Refer the text for additional details.