[Frontiers in Bioscience 14, 717-730, January 1, 2009]

Regulation of epithelial junctions by proteins of the ADP-ribosylation factor family

Toyoko Hiroi

Johns Hopkins University School of Medicine, Division of Cardiology, 1721 East Madison Street, Ross Research Building Room 1167, Baltimore, MD 21205


1. Abstract
2. Introduction
3. ADP-ribosylation factor (ARF) family
3.1. ARFs
3.2. Regulators of ARFs: guanine nucleotide exchange factors and GTPase-activating proteins
3.3. Functional properties of ARFs
4. Tight junctions
5. Adherens junctions
5.1. E-cadherin
5.2. Alpha-Catenin
5.3. Vinculin and alpha-Actinin
6. Desmosomes
7. Focal adhesions
7.1. Integrin
7.2. Filamin
7.3. Other proteins associated with focal adhesions
8. Cytoskeleton
8.1. Actin
8.2. Intermediate filament
9. Concluding remarks
10. Acknowledgment
11. References


ADP-ribosylation factor (ARF) proteins play a pivotal role in the regulation of membrane traffic and the organization of the cytoskeleton that are crucial to fundamental cellular processes, such as intracellular sorting/trafficking of newly synthesized proteins and endocytosis/exocytosis. In epithelial junctions, the ARF proteins are intimately associated with the dynamics of transmembrane proteins, such as E-cadherin and beta-1 integrin, and the adaptor proteins such as paxillin. In addition, ARF proteins play a key regulatory role in the remodeling of actin cytoskeleton necessary for the formation of membrane ruffles and protrusions in association with phospholipase D and members of the Rho GTPase family. These activities of ARF proteins influence not only the formation, stability and functional integrity of epithelial junctions but also the cell motility as well. In this review, I have attempted to provide a compendium of evidence that has contributed to our evolving understanding of these ARF proteins as well as their regulators (guanine nucleotide exchange factors and GTPase-activating proteins) in the regulation of epithelial junctions. In addition, I also have also highlighted potential mechanisms as to how these intricate regulatory pathways are regulated both spatially and temporally.