Trends in Cell Biology
Volume 11, Issue 12, 1 December 2001, Pages 483-486
Journal home page for Trends in Cell Biology

Review
Protein trafficking in the exocytic pathway of polarized epithelial cells

https://doi.org/10.1016/S0962-8924(01)02145-6Get rights and content

Abstract

Ten years ago, we knew much about the function of polarized epithelia from the work of physiologists, but, as cell biologists, our understanding of how these cells were constructed was poor. We knew proteins were sorted and targeted to different plasma membrane domains and that, in some cells, the Golgi was the site of sorting, but we did not know the mechanisms involved. Between 1991 and the present, significant advances were made in defining sorting motifs for apical and basal-lateral proteins, describing the sorting machinery in the trans-Golgi network (TGN) and plasma membrane, and in understanding how cells specify delivery of transport vesicles to different membrane domains. The challenge now is to extend this knowledge to defining molecular mechanisms in detail in vitro and comprehending the development of complex epithelial structures in vivo.

Section snippets

Sorting and transport of proteins to apical and basal-lateral membrane domains

The legacy of studies from the 1980s was a general belief that newly synthesized proteins were sorted in the Golgi complex and delivered to either the apical or basal-lateral membrane (Fig. 1); a complication, however, was a study in hepatocytes in situ that showed clearly that the site of sorting was the plasma membrane 2. The sorting mechanisms and basis for different sorting locations were unknown. It was suggested that apical sorting might be mediated by lipid sorting in the TGN, a

Specifying correct delivery of transport vesicles to different membrane domains

Delivery of transport vesicles from the TGN to different plasma membrane domains has a remarkably high fidelity. Such fidelity could be based on vesicles targeting along the cytoskeleton, and/or by specifying vesicle docking and fusion with the correct membrane domain (Fig. 1). Surprisingly, the fidelity of vesicle transport from the TGN to either the apical or basal-lateral membrane domain requires neither an intact actin or microtubule cytoskeleton 37. However, the efficiency of delivery is

Protein sorting at the plasma membrane

Although a perception is that targeting of proteins from the TGN to specific membrane domains is sufficient to generate cell-surface polarity, it is clear that cells have developed additional mechanisms to control protein distributions at the plasma membrane. The plasma membrane is turned over rapidly by endocytosis, and proteins must either be excluded selectively from internalization or, following internalization, be resorted to the correct membrane domain.

Assembly of the fodrin-based

The next 10 years

One big difference in this field now, compared with 10 years ago, is that a greater variety of approaches, experimental systems and disciplines are focusing on epithelial cell polarity. Now, studies in Drosophila and Caenorhabditis elegans are asking how polarized epithelial cells develop in vivo and are using genetic screens to identify new components of signaling pathways that regulate the formation of epithelial sheets (for example, see Ref. 47). Physiologists are examining how protein

Acknowledgements

We apologize to our colleagues for omitting many references that detail the studies reported in this review owing to space constraints. Work from the Nelson laboratory is supported by a grant from the National Institutes of Health to W.J.N. (GM35527), and C.Y. was also supported by a Walter V. and Idun Y. Berry Fellowship.

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