Insulin regulates alveolar epithelial function by inducing Na+/K+-ATPase translocation to the plasma membrane in a process mediated by the action of Akt

Alejandro P Comellas; Aileen M Kelly; Humberto E Trejo; Arturo Briva; Joyce Lee; Jacob I Sznajder; Laura A Dada

doi:10.1242/jcs.066464

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Insulin regulates alveolar epithelial function by inducing Na+/K+-ATPase translocation to the plasma membrane in a process mediated by the action of Akt

Journal article

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Insulin regulates alveolar epithelial function by inducing Na+/K+-ATPase translocation to the plasma membrane in a process mediated by the action of Akt

Alejandro P Comellas, Aileen M Kelly, Humberto E Trejo, Arturo Briva, Joyce Lee, Jacob I Sznajder and Laura A Dada

Journal of cell science, Vol.123(Pt 8), pp.1343-1351

04/15/2010

DOI: 10.1242/jcs.066464

PMCID: PMC2848117

PMID: 20332111

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Abstract

Stimulation of Na(+)/K(+)-ATPase translocation to the cell surface increases active Na(+) transport, which is the driving force of alveolar fluid reabsorption, a process necessary to keep the lungs free of edema and to allow normal gas exchange. Here, we provide evidence that insulin increases alveolar fluid reabsorption and Na(+)/K(+)-ATPase activity by increasing its translocation to the plasma membrane in alveolar epithelial cells. Insulin-induced Akt activation is necessary and sufficient to promote Na(+)/K(+)-ATPase translocation to the plasma membrane. Phosphorylation of AS160 by Akt is also required in this process, whereas inactivation of the Rab GTPase-activating protein domain of AS160 promotes partial Na(+)/K(+)-ATPase translocation in the absence of insulin. We found that Rab10 functions as a downstream target of AS160 in insulin-induced Na(+)/K(+)-ATPase translocation. Collectively, these results suggest that Akt plays a major role in Na(+)/K(+)-ATPase intracellular translocation and thus in alveolar fluid reabsorption.

Alveolar Epithelial Cells - drug effects

Alveolar Epithelial Cells - enzymology

Animals

Body Fluids - drug effects

Body Fluids - enzymology

Cattle

Cell Membrane - drug effects

Cell Membrane - enzymology

GTPase-Activating Proteins - metabolism

Humans

Insulin - pharmacology

Male

Phosphatidylinositol 3-Kinases - metabolism

Protein Transport - drug effects

Proto-Oncogene Proteins c-akt - metabolism

rab GTP-Binding Proteins - metabolism

Rats

Rats, Sprague-Dawley

Sodium-Potassium-Exchanging ATPase - metabolism

Subcellular Fractions - drug effects

Subcellular Fractions - enzymology

Details

Title: Subtitle: Insulin regulates alveolar epithelial function by inducing Na+/K+-ATPase translocation to the plasma membrane in a process mediated by the action of Akt
Creators: Alejandro P Comellas - Northwestern University
Aileen M Kelly - Northwestern University
Humberto E Trejo - Northwestern University
Arturo Briva - Northwestern University
Joyce Lee - Northwestern University
Jacob I Sznajder - Northwestern University
Laura A Dada - Northwestern University
Resource Type: Journal article
Publication Details: Journal of cell science, Vol.123(Pt 8), pp.1343-1351
DOI: 10.1242/jcs.066464
PMID: 20332111
PMCID: PMC2848117
ISSN: 0021-9533
eISSN: 1477-9137
Grant note: R01 HL048129 / NHLBI NIH HHS K01 HL080966 / NHLBI NIH HHS R37 HL048129 / NHLBI NIH HHS K01HL080966 / NHLBI NIH HHS
Language: English
Date published: 04/15/2010
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; ICTS; Internal Medicine
Record Identifier: 9984359924402771

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