The Integrin β1 Subunit Regulates Paracellular Permeability of Kidney Proximal Tubule Cells

• Published in: The Journal of biological chemistry Vol. 289; no. 12; pp. 8532 - 8544
• Main Authors: Elias, Bertha C., Mathew, Sijo, Srichai, Manakan B., Palamuttam, Riya, Bulus, Nada, Mernaugh, Glenda, Singh, Amar B., Sanders, Charles R., Harris, Raymond C., Pozzi, Ambra, Zent, Roy
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.03.2014; American Society for Biochemistry and Molecular Biology
• Subjects: Adherens Junction; Animals; Cadherins - genetics; Cadherins - metabolism; Cell Biology; Cell Membrane Permeability; Cells, Cultured; Claudin-2 - genetics; Claudin-2 - metabolism; Down-Regulation; E-cadherin; Epithelial Cell; Epithelial Cells - metabolism; Gene Deletion; Integrin beta1 - analysis; Integrin beta1 - genetics; Integrin beta1 - metabolism; Kidney Tubules, Proximal - cytology; Kidney Tubules, Proximal - metabolism; Mice; Permeability; Renal Physiology; Tight Junctions; Up-Regulation; Urine - chemistry; Epithelial Cell; Adherens Junction; Renal Physiology; E-cadherin; Tight Junctions
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M113.526509

Epithelial cells lining the gastrointestinal tract and kidney have different abilities to facilitate paracellular and transcellular transport of water and solutes. In the kidney, the proximal tubule allows both transcellular and paracellular transport, while the collecting duct primarily facilitates transcellular transport. The claudins and E-cadherin are major structural and functional components regulating paracellular transport. In this study we present the novel finding that the transmembrane matrix receptors, integrins, play a role in regulating paracellular transport of renal proximal tubule cells. Deleting the integrin β1 subunit in these cells converts them from a “loose” epithelium, characterized by low expression of E-cadherin and claudin-7 and high expression of claudin-2, to a “tight” epithelium with increased E-cadherin and claudin-7 expression and decreased claudin-2 expression. This effect is mediated by the integrin β1 cytoplasmic tail and does not entail β1 heterodimerization with an α-subunit or its localization to the cell surface. In addition, we demonstrate that deleting the β1 subunit in the proximal tubule of the kidney results in a major urine-concentrating defect. Thus, the integrin β1 tail plays a key role in regulating the composition and function of tight and adherens junctions that define paracellular transport properties of terminally differentiated renal proximal tubule epithelial cells. Background: Proximal tubule kidney epithelial cells differentiate into a “loose” epithelium by unknown mechanisms. Results: Deleting integrin β1 converts proximal tubule cells from a “loose” to a “tight” epithelium. Conclusion: Integrin β1 regulates the composition and function of tight and adherens junctions that define paracellular transport properties of proximal tubule epithelial cells. Significance: Integrins might regulate terminal differentiation of polarized epithelial cells.