AbstractsBiology & Animal Science

Regulation of endothelial cell-cell junctions and vascular permeability by Rho GEFs and GAPs

by K.D. Prummel




Institution: Universiteit Utrecht
Department:
Year: 2014
Keywords: endothelial permeability; Rho GTPases; Rho GEFs; Rho GEFs; cell-cell junction regulation
Record ID: 1259885
Full text PDF: http://dspace.library.uu.nl:8080/handle/1874/291004


Abstract

The endothelial monolayer covers the luminal side of blood and lymphatic vessels and functions as a physical barrier. The cell-cell junctions between the endothelial cells are important to regulate and maintain the barrier function. Adherens and tight junctions, the main adhesion molecules found in endothelial cells, are regulated by Rho GTPases RhoA, Rac1 and Cdc42. All three Rho GTPases can either induce endothelial permeability as protect the barrier, depending on their spatiotemporal activation and upstream regulators. Rho GTPases are regulated by several guanine exchange factors (GEFs) and GTPase activating proteins (GAPs), which switch the GTPases between the active GTP-bound state and the inactive GDP-bound state respectively. In turn, GEFs and GEFs are under control of inflammatory cytokines and vascular growth factors. In this review is outlined which GEFs and GAPs are associated with the regulation of cellular junctions. For some GEFs/GAPs is already established that they control the vascular permeability in vivo. A specific attention is given to GEFs/GAPs involved in the regulation of junctions in other cell types, but known to be expressed in endothelium. It is important to unravel how GEFs/GAPs are activated and what their subcellular localization is, this will give more insight in the complex regulation of Rho GTPases.