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.

Core-glycosylated Mucin-like Repeats from MUC1 Are an Apical Targeting Signal

“…Alternatively, glycan-dependent sorting receptors, possibly galectins, have been suggested to facilitate sorting (9,38,39). Segregation of apically and basolaterally destined proteins first occurs in the trans-Golgi network, although many proteins subsequently traverse endocytic compartments prior to reaching the cell surface (40,41). Apical proteins that associate with glycolipid-enriched rafts apparently traffic through apical early endosomes, whereas non-raft-associated proteins may enter the ARE prior to surface delivery (31,42,43).…”

Role of the epithelial cell-specific clathrin adaptor complex AP-1B in cell polarity

“…Although the mechanisms are not understood as yet, the interaction between AP-1B and the PtdIns(4) P 5-kinase PtdInsPKIg-90 may be involved in generating the PtdIns (3,4,5)P 3 precursor PtdIns(4,5)P 2 from PtdIns(4)P. 64 PtdIns(4)P may be delivered to REs with vesicles originating at the TGN. 7 Notably, Arf6 also recruits and activates PtdInsPKIg-90 providing additional hints that PtdInsPKIg-90 may play a role in PtdIns(3,4,5)P 3 formation in REs. 46 Indeed, overexpression of mutant Arf6 in MDCK cells led to a mild albeit significant reduction in PtdIns(3,4,5)P 3 levels in REs.…”

“…1, routes 9a and 9b). In addition, newly synthesized cargos such as VSVG may move from the TGN into REs during biosynthetic delivery 6,7 ( Fig. 1, route 3).…”

Endosomal system genetics and autism spectrum disorders: A literature review

“…For example, neuronal and epithelial endosomal systems are polarized, creating a more diverse and specialized pathway in order to accomplish their cellular functions (Yap and Winckler, 2012). The recycling endosomal system within neurons is highly specialized and differs in its ability to sort receptors as well as recruit binding partners (Folsch et al, 2009). Due to the spatial architecture of neurons, their recycling endosomal system has been found throughout the soma as well as in the dendrites and axons.…”