The role of secretory and endocytic pathways in the maintenance of cell polarity

Abstract

Epithelial cells line virtually every organ cavity in the body and are important for vectorial transport through epithelial monolayers such as nutrient uptake or waste product excretion. Central to these tasks is the establishment of epithelial cell polarity. During organ development, epithelial cells set up two biochemically distinct plasma membrane domains, the apical and the basolateral domain. Targeting of correct constituents to each of these regions is essential for maintaining epithelial cell polarity. Newly synthesized transmembrane proteins destined for the basolateral or apical membrane domain are sorted into separate transport carriers either at the TGN (trans-Golgi network) or in perinuclear REs (recycling endosomes). After initial delivery, transmembrane proteins, such as nutrient receptors, frequently undergo multiple rounds of endocytosis followed by re-sorting in REs. Recent work in epithelial cells highlights the REs as a potent sorting station with different subdomains representing individual targeting zones that facilitate the correct surface delivery of transmembrane proteins.

Figure 1. Model of different sorting pathways in a polarized epithelial cell

The sorting of biosynthetic cargos to different plasma membrane domains occurs either at the trans-Golgi network (TGN) or in the recycling endosome (RE) in a polarized epithelial cell. Arrows indicate the direction of movement of representative cargos at various compartments. AEE, apical early endosomes; BEE, basolateral early endosomes; BBSome, octameric complex of Bardet-Biedl syndrome proteins; PIP₃, PI(3,4,5)P₃; TfnR, transferrin receptor. Question marks denote pathways that are not proven yet.