Rab1 GTPase promotes expression of β-adrenergic receptors in rat pulmonary microvascular endothelial cells

Yuncheng Li, Guansong Wang, Kexiong Lin, Hongjin Yin, Changxi Zhou, Ting Liu, Guangyu Wu, Guisheng Qian

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

It is known that Rab1 regulates the expression and function of beta-adrenoceptors (β-ARs) in many cells. However, the effect of these changes in rat pulmonary microvascular endothelial cells (RPMVECs) is not known. In the present study, we investigated the role of Rab1, a Ras-like GTPase that coordinates protein transport from the endoplasmic reticulum (ER) to the Golgi body and regulates the cell-surface targeting and function of endogenous β-ARs in RPMVECs in the presence of lipopolysaccharide (LPS). We found that lentivirus-driven expression of wild-type Rab1 (Rab1WT) in RPMVECs strongly enhanced the amount of β-ARs on the cell surface, whereas the dominant-negative mutant Rab1N124I significantly attenuated β-ARs expression on the cell surface. In addition, LPS stimulation significantly reduced β-ARs expression on the cell surface in RPMVECs; however, this effect was reversed by over-expression of wild-type Rab1WT. Fluorescent microscopy analysis demonstrated that expression of Rab1N124I and Rab1 small interfering RNA (siRNA) significantly induced the accumulation of green fluorescent protein (GFP)-tagged β2-AR in the ER. Consistent with their effects on β-ARs export, Rab1WT and Rab1N124I differentially modified the β-AR-mediated activation of extracellular signal-regulated kinase1/2 (ERK1/2). Importantly, over-expression of Rab1WT markedly reduced LPS-induced hyper-permeability of RPMVECs by increasing the expression of β2-AR on the cell surface. These data reveal that β-ARs function in RPMVECs could be modulated by manipulating β-ARs traffic from the ER to the Golgi body. We propose the ER-to-Golgi transport as a regulatory site for control of permeability of RPMVECs.

Original languageEnglish (US)
Pages (from-to)1201-1209
Number of pages9
JournalInternational Journal of Biochemistry and Cell Biology
Volume42
Issue number7
DOIs
StatePublished - Jul 2010
Externally publishedYes

Keywords

  • Beta-adrenergic receptors
  • Lipopolysaccharide
  • Permeability
  • Rab1 GTPase
  • Small interfering RNA

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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