A current overview of RhoA, RhoB, and RhoC functions in vascular biology and pathology

Abstract

The Rho subfamily members of Rho GTPases, RhoA, RhoB, and RhoC, are key regulators of signal transduction in a variety of cellular processes, including regulation of actomyosin and microtubule dynamics, cell shape, cell adhesion, cell division, cell migration, vesicle/membrane trafficking, and cell proliferation. Traditionally, the focus of research on RhoA/B/C has been on tumor biology, as dysregulation of expression or function of these proteins plays an important role in the pathogenesis of various cancer entities. However, RhoA, RhoB, and RhoC are also important in the context of vascular biology and pathology because they influence endothelial barrier function, vascular smooth muscle contractility and proliferation, vascular function and remodelling as well as angiogenesis. In this context, RhoA/B/C exploit numerous effector molecules to transmit their signals, and their activity is regulated by a variety of guanine nucleotide exchange factors (RhoGEFs) and GTPase-activating proteins (RhoGAPs) that enable precise spatiotemporal activation often in concert with other Rho GTPases. Although their protein structure is very similar, different mechanisms of regulation of gene expression, different localization, and to some extent different interaction with RhoGAPs and RhoGEFs have been observed for RhoA/B/C. In this review, we aim to provide a current overview of the Rho subfamily as regulators of vascular biology and pathology, analyzing database information and existing literature on expression, protein structure, and interaction with effectors and regulatory proteins. In this setting, we will also discuss recent findings on Rho effectors, RhoGEFs, RhoGAPs, as well as guanine nucleotide dissociation inhibitors (RhoGDIs).