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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

The purpose of this study was to define the role of the Rho family of small GTPases in the β-adrenergic regulation of the Na,K-ATPase in alveolar epithelial cells (AEC). The β-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 β2-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 β 2-adrenergic receptor, Gs, PKA, Gi, RhoA, and ROCK.

Original languageEnglish (US)
Pages (from-to)3888-3897
Number of pages10
JournalMolecular biology of the cell
Volume14
Issue number9
DOIs
StatePublished - Sep 1 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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