Apical trafficking in epithelial cells: signals, clusters and motors

Abstract

In the early days of epithelial cell biology, researchers working with kidney and/or intestinal epithelial cell lines and with hepatocytes described the biosynthetic and recycling routes followed by apical and basolateral plasma membrane (PM) proteins. They identified the trans-Golgi network and recycling endosomes as the compartments that carried out apical-basolateral sorting. They described complex apical sorting signals that promoted association with lipid rafts, and simpler basolateral sorting signals resembling clathrin-coated-pit endocytic motifs. They also noticed that different epithelial cell types routed their apical PM proteins very differently, using either a vectorial (direct) route or a transcytotic (indirect) route. Although these original observations have generally held up, recent studies have revealed interesting complexities in the routes taken by apically destined proteins and have extended our understanding of the machinery required to sustain these elaborate sorting pathways. Here, we critically review the current status of apical trafficking mechanisms and discuss a model in which clustering is required to recruit apical trafficking machineries. Uncovering the mechanisms responsible for polarized trafficking and their epithelial-specific variations will help understand how epithelial functional diversity is generated and the pathogenesis of many human diseases.

Identification of the roles of conserved charged residues in the extracellular domain of an epithelial sodium channel (ENaC) subunit by alanine mutagenesis

“…The proteins are then probably packaged in vesicular endosomes that are directed to the apical membrane (5,36). Studies on a variety of apical proteins have revealed several alternative routes of vesicular trafficking (41). In some cell types, ENaC appear to be transported in membrane lipid raft domains (5).…”

“…These proteins include SNARE type proteins such as syntaxin (3), Rab GTPases (29), and G proteins (17). The list of proteins involved is probably longer than we currently recognize (41).…”

Reduced Immunoglobulin A Transcytosis Associated with Immunoglobulin A Nephropathy and Nasopharyngeal Carcinoma

“…4). This suggests that the reduction in pIgR-A580V transcytosis is likely due to reduced cleavage (13,16,17). …”

Mophogenesis and Dynamics of Post-Golgi Transport Carriers

“…This appears not to be a case, as a number of proteins (such as VSVG and the LDL receptor) have been reported to use a Rab8-positive sub-population of endosomes as an intermediate station on their way to the basolateral PM in epithelial cells (Ang et al, 2004), while others cargoes (such as E-cadherin, for example) move to the PM through a Rab11-containing endocytic compartment (Lock and Stow, 2005). Furthermore, ablation of the different endocytic compartments through horseradish peroxidase (HRP)-catalyzed crosslinking has revealed a number of apical proteins to take various through-endosome routes to reach the cell surface (Weisz and Rodriguez-Boulan, 2009). It remains to be understood, however, whether any cross-talk between these routes exists.…”