Journal article
A novel pathway spatiotemporally activates Rac1 and redox signaling in response to fluid shear stress
The Journal of cell biology, Vol.201(6), pp.863-873
06/10/2013
DOI: 10.1083/jcb.201207115
PMCID: PMC3678169
PMID: 23733346
Abstract
Hemodynamic forces regulate embryonic organ development, hematopoiesis, vascular remodeling, and atherogenesis. The mechanosensory stimulus of blood flow initiates a complex network of intracellular pathways, including activation of Rac1 GTPase, establishment of endothelial cell (EC) polarity, and redox signaling. The activity of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase can be modulated by the GTP/GDP state of Rac1; however, the molecular mechanisms of Rac1 activation by flow are poorly understood. Here, we identify a novel polarity complex that directs localized Rac1 activation required for downstream reactive oxygen species (ROS) production. Vav2 is required for Rac1 GTP loading, whereas, surprisingly, Tiam1 functions as an adaptor in a VE-cadherin–p67phox–Par3 polarity complex that directs localized activation of Rac1. Furthermore, loss of Tiam1 led to the disruption of redox signaling both in vitro and in vivo. Our results describe a novel molecular cascade that regulates redox signaling by the coordinated regulation of Rac1 and by linking components of the polarity complex to the NADPH oxidase.
Details
- Title: Subtitle
- A novel pathway spatiotemporally activates Rac1 and redox signaling in response to fluid shear stress
- Creators
- Yunhao Liu - Department of Cell Biology and Physiology, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599Caitlin Collins - Department of Cell Biology and Physiology, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599William B Kiosses - Core Microscopy Facility, The Scripps Research Institute, La Jolla, CA 92037Ann M Murray - Department of Biochemistry and Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242Monika Joshi - Department of Biochemistry and Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242Tyson R Shepherd - Department of Biochemistry and Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242Ernesto J Fuentes - Department of Biochemistry and Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, Department of Biochemistry and Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242Ellie Tzima - Department of Cell Biology and Physiology, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
- Resource Type
- Journal article
- Publication Details
- The Journal of cell biology, Vol.201(6), pp.863-873
- DOI
- 10.1083/jcb.201207115
- PMID
- 23733346
- PMCID
- PMC3678169
- ISSN
- 0021-9525
- eISSN
- 1540-8140
- Language
- English
- Date published
- 06/10/2013
- Academic Unit
- Biochemistry and Molecular Biology
- Record Identifier
- 9984024514302771
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