Regulation of β-adrenergic receptor trafficking and lung microvascular endothelial cell permeability by Rab5 GTPase

Junjun Yang, Huan Sun, Jihang Zhang, Mingdong Hu, Jianchun Wang, Guangyu Wu, Guansong Wang

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Rab5 GTPase modulates the trafficking of the cell surface receptors, including G protein-coupled β-adrenergic receptors (β-ARs). Here, we have determined the role of Rab5 in regulating the internalization of β-ARs in lung microvascular endothelial cells (LMECs) and in maintaining the integrity and permeability of endothelial cell barrier. Our data demonstrate that lipopolysaccharide (LPS) treatment disrupts LMEC barrier function and reduces the cell surface expression of β-ARs. Furthermore, the activation of β-ARs, particularly β2-AR, is able to protect the LMEC permeability from LPS injury. Moreover, siRNA-mediated knockdown of Rab5 inhibits both the basal and agonist-provoked internalization of β-ARs, therefore, enhancing the cell surface expression of the receptors and receptor-mediated ERK1/2 activation. Importantly, knockdown of Rab5 not only inhibits the LPS-induced effects on β-ARs but also protects the LMEC monolayer permeability. All together, these data provide strong evidence indicating a crucial role of Rab5-mediated internalization of β-ARs in functional regulation of LMECs.

Original languageEnglish (US)
Pages (from-to)868-878
Number of pages11
JournalInternational Journal of Biological Sciences
Volume11
Issue number8
DOIs
StatePublished - Jun 1 2015

Keywords

  • Internalization
  • Lipopolysaccharide
  • Lung
  • Microvascular endothelial cell
  • Permeability
  • Rab5
  • Small interfering RNA
  • Trafficking
  • β-adrenergic receptor

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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