title: Rho GAPs and GEFs: controling switches in endothelial cell adhesion.
abstract: Within blood vessels, endothelial cellâ€"cell and cellâ€"matrix adhesions are crucial to preserve barrier function, and these adhesions are tightly controlled during vascular development, angiogenesis, and transendothelial migration of inflammatory cells. Endothelial cellular signaling that occurs via the family of Rho GTPases coordinates these cell adhesion structures through cytoskeletal remodelling. In turn, Rho GTPases are regulated by GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs). To understand how endothelial cells initiate changes in the activity of Rho GTPases, and thereby regulate cell adhesion, we will discuss the role of Rho GAPs and GEFs in vascular biology. Many potentially important Rho regulators have not been studied in detail in endothelial cells. We therefore will first overview which GAPs and GEFs are highly expressed in endothelium, based on comparative gene expression analysis of human endothelial cells compared with other tissue cell types. Subsequently, we discuss the relevance of Rho GAPs and GEFs for endothelial cell adhesion in vascular homeostasis and disease.
authors.affiliation: Department of Molecular Cell Biology; Sanquin Research and Swammerdam Institute for Life Sciences; University of Amsterdam; The Netherlands.
authors.forename: Jaap D
authors.initials: JD
authors.lastname: van Buul
authors.affiliation: Department of Pediatric Oncology/Hematology; Erasmus University Medical Center; Rotterdam, The Netherlands.
authors.forename: Dirk
authors.initials: D
authors.lastname: Geerts
authors.affiliation: Department of Molecular Cell Biology; Sanquin Research and Swammerdam Institute for Life Sciences; University of Amsterdam; The Netherlands.
authors.forename: Stephan
authors.initials: S
authors.lastname: Huveneers
mesh_terms: D002448:Cell Adhesion / Q000235:genetics*; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; C085379:rho GTPase-activating protein; D020741:rho GTP-Binding Proteins
keywords: Cdc42; GDI; Rac; Rho GTPase; VE-cadherin; adherens junction; adhesion; angiogenesis; inflammation; integrin