Trafficking to the apical and basolateral membranes in polarized epithelial cells

Abstract

Renal epithelial cells must maintain distinct protein compositions in their apical and basolateral membranes in order to perform their transport functions. The creation of these polarized protein distributions depends on sorting signals that designate the trafficking route and site of ultimate functional residence for each protein. Segregation of newly synthesized apical and basolateral proteins into distinct carrier vesicles can occur at the trans-Golgi network, recycling endosomes, or a growing assortment of stations along the cellular trafficking pathway. The nature of the specific sorting signal and the mechanism through which it is interpreted can influence the route a protein takes through the cell. Cell type-specific variations in the targeting motifs of a protein, as are evident for Na,K-ATPase, demonstrate a remarkable capacity to adapt sorting pathways to different developmental states or physiologic requirements. This review summarizes our current understanding of apical and basolateral trafficking routes in polarized epithelial cells.

Keywords: cell and transport physiology; epithelial; renal cell biology.

Figure 1.

Apical and basolateral proteins pursue multiple biosynthetic routes to the plasma membrane following their exit from the TGN. This model depicts these routes as well as some endocytic pathways. Proteins targeted to the basolateral membrane can traffic directly from the TGN (1), or traffic through endosomes (2) before surface delivery (3).^, A similar direct route for apical proteins has not been observed. Endocytosed basolateral proteins traffic through the basolateral early endosome (BEE, 3) and CRE before recycling or degradation. Apically directed proteins traverse the apical early endosome (AEE, 4a and b) or the apical recycling endosome (ARE, 5a and b) before apical delivery. GPI-linked proteins, influenza HA protein, and other raft-dependent proteins traverse the AEE,^, while proteins such as endolyn and MUC1, whose trafficking depends on glycan residues, traffic through the ARE.^, Conversely, lactase phlorizin hydrolase and sucrase isomalatase traffic between the apical early and apical recycling endosomes (6). Proteins internalized from the apical membrane to the AEE can traffic to the ARE for recycling back to the surface, or to the CRE and late endosomes if they are targeted for degradation (unlabeled arrows). LE, late endosome; lys, lysosome; MVB, multivesicular body.

Figure 2.

Na,K-ATPase displays distinct polarized localization in different tissues and developmental stages. (A–C) Immunolocalization of sodium pump α-subunit in murine choroid plexus (A), developing kidney (B), and adult kidney (C). Arrowheads indicate apical localization of α-subunit. Arrows indicate basolateral localization of α-subunit. (A) Sodium pump α-subunit localizes to the apical membrane of choroid plexus cells. (B) In developing kidneys harvested from embryonic day 17 mice, sodium pump α-subunit localizes to the apical membrane of the epithelial cells of the renal vesicles, which are the earliest structures in nephrogenesis. In newly developing collecting ducts, sodium pump α-subunit localizes to both apical and basolateral membranes or—in more mature collecting ducts—to basolateral membranes only. (C) Sodium pump α-subunit localizes to the basolateral infoldings of adult kidney tubules. (D–F) Schematic views of sodium pump localization in choroid plexus (D), the developing kidney (E), and the adult kidney (F). Sodium pump α-subunit is depicted in red. Bar=10 μm.