The integrin β1 subunit regulates paracellular permeability of kidney proximal tubule cells

Bertha C. Elias, Sijo Mathew, Manakan B. Srichai, Riya Palamuttam, Nada Bulus, Glenda Mernaugh, Amar Bahadur Singh, Charles R. Sanders, Raymond C. Harris, Ambra Pozzi, Roy Zent

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)8532-8544
Number of pages13
JournalJournal of Biological Chemistry
Volume289
Issue number12
DOIs
StatePublished - Mar 21 2014

Fingerprint

Proximal Kidney Tubule
Transcytosis
Integrins
Permeability
Claudin-2
Cadherins
Epithelium
Epithelial Cells
Claudins
Kidney
Adherens Junctions
Tight Junctions
Linings
Transport properties
Ducts
Gastrointestinal Tract
Urine
Defects
Water
Chemical analysis

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Elias, B. C., Mathew, S., Srichai, M. B., Palamuttam, R., Bulus, N., Mernaugh, G., ... Zent, R. (2014). The integrin β1 subunit regulates paracellular permeability of kidney proximal tubule cells. Journal of Biological Chemistry, 289(12), 8532-8544. https://doi.org/10.1074/jbc.M113.526509

The integrin β1 subunit regulates paracellular permeability of kidney proximal tubule cells. / Elias, Bertha C.; Mathew, Sijo; Srichai, Manakan B.; Palamuttam, Riya; Bulus, Nada; Mernaugh, Glenda; Singh, Amar Bahadur; Sanders, Charles R.; Harris, Raymond C.; Pozzi, Ambra; Zent, Roy.

In: Journal of Biological Chemistry, Vol. 289, No. 12, 21.03.2014, p. 8532-8544.

Research output: Contribution to journalArticle

Elias, BC, Mathew, S, Srichai, MB, Palamuttam, R, Bulus, N, Mernaugh, G, Singh, AB, Sanders, CR, Harris, RC, Pozzi, A & Zent, R 2014, 'The integrin β1 subunit regulates paracellular permeability of kidney proximal tubule cells', Journal of Biological Chemistry, vol. 289, no. 12, pp. 8532-8544. https://doi.org/10.1074/jbc.M113.526509
Elias BC, Mathew S, Srichai MB, Palamuttam R, Bulus N, Mernaugh G et al. The integrin β1 subunit regulates paracellular permeability of kidney proximal tubule cells. Journal of Biological Chemistry. 2014 Mar 21;289(12):8532-8544. https://doi.org/10.1074/jbc.M113.526509
Elias, Bertha C. ; Mathew, Sijo ; Srichai, Manakan B. ; Palamuttam, Riya ; Bulus, Nada ; Mernaugh, Glenda ; Singh, Amar Bahadur ; Sanders, Charles R. ; Harris, Raymond C. ; Pozzi, Ambra ; Zent, Roy. / The integrin β1 subunit regulates paracellular permeability of kidney proximal tubule cells. In: Journal of Biological Chemistry. 2014 ; Vol. 289, No. 12. pp. 8532-8544.
@article{65aa6c69bcf54d7c9e12c4dcf82ac06a,
title = "The integrin β1 subunit regulates paracellular permeability of kidney proximal tubule cells",
abstract = "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.",
author = "Elias, {Bertha C.} and Sijo Mathew and Srichai, {Manakan B.} and Riya Palamuttam and Nada Bulus and Glenda Mernaugh and Singh, {Amar Bahadur} and Sanders, {Charles R.} and Harris, {Raymond C.} and Ambra Pozzi and Roy Zent",
year = "2014",
month = "3",
day = "21",
doi = "10.1074/jbc.M113.526509",
language = "English (US)",
volume = "289",
pages = "8532--8544",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "12",

}

TY - JOUR

T1 - The integrin β1 subunit regulates paracellular permeability of kidney proximal tubule cells

AU - Elias, Bertha C.

AU - Mathew, Sijo

AU - Srichai, Manakan B.

AU - Palamuttam, Riya

AU - Bulus, Nada

AU - Mernaugh, Glenda

AU - Singh, Amar Bahadur

AU - Sanders, Charles R.

AU - Harris, Raymond C.

AU - Pozzi, Ambra

AU - Zent, Roy

PY - 2014/3/21

Y1 - 2014/3/21

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84896931147&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84896931147&partnerID=8YFLogxK

U2 - 10.1074/jbc.M113.526509

DO - 10.1074/jbc.M113.526509

M3 - Article

VL - 289

SP - 8532

EP - 8544

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 12

ER -