[Frontiers in Bioscience 14, 2130-2148, January 1, 2009]

Na,K-ATPase and epithelial tight junctions

Sigrid A. Rajasekaran, Ayyappan K. Rajasekaran

Nemours Center for Childhood Cancer Research, Alfred I. DuPont Hospital for Children, Wilmington, DE 19803

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Tight junctions
4. Na,K-ATPase
4.1. Functions, subunits and isoforms
4.2. Regulation and interaction with other proteins
4.3. Na,K-ATPase as a signaling molecule
5. Na,K-ATPase and tight junctions
6. Na,K-ATPase in the development of tight junctions
6.1. Na,K-ATPase in blastocyst development
6.2. Na,K-ATPase in zebrafish
6.3. Drosophila and septate junctions
7. Future Perspectives
7.1. Na,K-ATPase, a member of the tight junction protein complex
7.2. Na,K-ATPase b-subunit, a cell adhesion molecule
7.3. Na,K-ATPase, a signaling scaffold that regulates tight junctions
8. Sodium/ion homeostasis and tight junctions
9. A role for Na,K-ATPase in epithelial-mesenchymal transition (EMT) and cancer
10. Conclusions
11. Acknowledgements
12. References

1. ABSTRACT

Tight junctions are unique organelles in polarized epithelial and endothelial cells that regulate the flow of solutes and ions across the epithelial barrier. The structure and functions of tight junctions are regulated by a wide variety of signaling and molecular mechanisms. Several recent studies in mammals, drosophila, and zebrafish reported a new role for Na,K-ATPase, a well-studied ion transporter, in the modulation of tight junction development, permeability, and polarity. In this review, we have attempted to compile these new reports and suggest a model for a conserved role of Na,K-ATPase in the regulation of tight junction structure and functions.