The GTP-binding protein RhoA mediates Na,K-ATPase exocytosis in alveolar epithelial cells

Emilia Lecuona; Karen Ridge; Liuska Pesce; Daniel Batlle; Jacob I Sznajder

doi:10.1091/mbc.E02-12-0781

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The GTP-binding protein RhoA mediates Na,K-ATPase exocytosis in alveolar epithelial cells

Journal article

Open access

Peer reviewed

The GTP-binding protein RhoA mediates Na,K-ATPase exocytosis in alveolar epithelial cells

Emilia Lecuona, Karen Ridge, Liuska Pesce, Daniel Batlle and Jacob I Sznajder

Molecular biology of the cell, Vol.14(9), pp.3888-3897

09/2003

DOI: 10.1091/mbc.E02-12-0781

PMCID: PMC196585

PMID: 12972572

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Abstract

The purpose of this study was to define the role of the Rho family of small GTPases in the beta-adrenergic regulation of the Na,K-ATPase in alveolar epithelial cells (AEC). The beta-adrenergic receptor agonist isoproterenol (ISO) increased the Na,K-ATPase protein abundance at the plasma membrane and activated RhoA in a time-dependent manner. AEC pretreated with mevastatin, a specific inhibitor of prenylation, or transfected with the dominant negative RhoAN19, prevented ISO-mediated Na,K-ATPase exocytosis to the plasma membrane. The ISO-mediated activation of RhoA in AEC occurred via beta2-adrenergic receptors and involved Gs-PKA as demonstrated by incubation with the protein kinase A (PKA)-specific inhibitors H89 and PKI (peptide specific inhibitor), and Gi, as incubation with pertussis toxin or cells transfected with a minigene vector for Gi inhibited the ISO-mediated RhoA activation. However, cells transfected with minigene vectors for G12 and G13 did not prevent RhoA activation by ISO. Finally, the ISO-mediated Na,K-ATPase exocytosis was regulated by the Rho-associated kinase (ROCK), as preincubation with the specific inhibitor Y-27632 or transfection with dominant negative ROCK, prevented the increase in Na,K-ATPase at the plasma membrane. Accordingly, ISO regulates Na,K-ATPase exocytosis in AEC via the activation of beta2-adrenergic receptor, Gs, PKA, Gi, RhoA, and ROCK.

Cyclic AMP-Dependent Protein Kinases - metabolism

Epithelial Cells - metabolism

Lovastatin - pharmacology

Humans

Adrenergic beta-Agonists - pharmacology

Cyclic AMP

Intracellular Signaling Peptides and Proteins

Models, Molecular

rhoA GTP-Binding Protein - metabolism

Lovastatin - analogs & derivatives

Exocytosis

Cell Membrane - enzymology

Sodium-Potassium-Exchanging ATPase - metabolism

Isoproterenol - pharmacology

rho-Associated Kinases

Cloning, Molecular

Fluorescent Antibody Technique

Receptors, Adrenergic, beta - drug effects

Tumor Cells, Cultured

Protein Prenylation - physiology

Receptors, Adrenergic, beta - metabolism

Protein-Serine-Threonine Kinases - metabolism

Details

Title: Subtitle: The GTP-binding protein RhoA mediates Na,K-ATPase exocytosis in alveolar epithelial cells
Creators: Emilia Lecuona - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University, Chicago, Illinois 60611, USA. e-lecuona@northwestern.edu
Karen Ridge
Liuska Pesce
Daniel Batlle
Jacob I Sznajder
Resource Type: Journal article
Publication Details: Molecular biology of the cell, Vol.14(9), pp.3888-3897
DOI: 10.1091/mbc.E02-12-0781
PMID: 12972572
PMCID: PMC196585
NLM abbreviation: Mol Biol Cell
ISSN: 1059-1524
eISSN: 1939-4586
Grant note: R01 HL048129 / NHLBI NIH HHS R37 HL048129 / NHLBI NIH HHS
Language: English
Date published: 09/2003
Academic Unit: Endocrinology and Diabetes; Stead Family Department of Pediatrics
Record Identifier: 9984093461002771

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