Microtubules regulate angiotensin II type 1 receptor and Rac1 localization in caveolae/lipid rafts: Role in redox signaling

Lian Zuo, Masuko Ushio-Fukai, Lula L. Hilenski, R. Wayne Alexander

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Objective-Microtubules are important in signal transduction temporal-spatial organization. Full expression of angiotensin II (Ang II) signaling in vascular smooth muscle cells (VSMCs) is dependent on the reactive oxygen species (ROS) derived from nicotinamide-adenine dinucleotide phosphate (NAD(P)H) oxidase and the dynamic association of the Ang II type I receptor (AT1R) with caveolae/lipid rafts. Translocation of the small GTPase Rac1 to the plasma membrane is an essential step for activation of NAD(P)H oxidase; however, its precise localization in the plasma membrane after agonist stimulation and how it is targeted are unknown. We hypothesized that microtubules are involved in regulating multiphasic Ang II signaling events in VSMC. Methods and Results-We show that Ang II promotes Rac1 and AT1R trafficking into caveolae/lipid rafts, which is blocked by disruption of microtubules with nocodazole. As a consequence, nocodazole significantly inhibits Ang II-stimulated H2O2 production, its downstream ROS-dependent epidermal growth factor receptor transactivation, Akt phosphorylation, and vascular hypertrophy without affecting Rac1 activation or ROS-independent extracellular signal-regulated kinase 1/2 phosphorylation. Conclusions-These results suggest that proper Rac1 and AT1R trafficking into caveolae/lipid rafts requires the integrity of microtubules and provide insight into the essential role of microtubules for the spatial-temporal organization of ROS-dependent and caveolae/lipid rafts-dependent AT1R signaling linked to vascular hypertrophy.

Original languageEnglish (US)
Pages (from-to)1223-1228
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume24
Issue number7
DOIs
StatePublished - Jul 2004
Externally publishedYes

Keywords

  • Angiotensin II
  • Caveolae
  • Microtubules
  • Reactive oxygen species
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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