title: Small rho GTPases regulate antigen presentation in dendritic cells.
abstract: Dendritic cells (DC) are involved in the regulation of innate and adaptive immunity. However, the molecular mechanisms maintaining DC function remain to be elucidated. In this study, we report on the role of small Rho GTPases: Cdc42, Rac1, and RhoA in the regulation of DC adherence, Ag presentation, migration, chemotaxis, and endocytosis. Murine DC were transfected with vaccinia virus-based constructs, encoding dominant-negative or constitutively active (ca) mutant forms of Rho GTPases. We demonstrate that Cdc42 plays a major role in the regulation of DC adhesion, because caCdc42-transfected DC had significant up-regulation of adhesion to extracellular matrix, which was blocked by the Rho GTPase inhibitor toxin B (ToxB). In contrast, caRho-transfected DC only modestly elevated DC adhesion, and caRac had no effect. Additionally, caCdc42 and caRho increased the ability of DC to present OVA peptide to specific T cells. This effect was abrogated by ToxB. Activation of Cdc42 in DC significantly inhibited spontaneous and chemokine-induced DC migration. Furthermore, uptake of dextran 40 by DC was significantly enhanced by Rho GTPase activators cytotoxic necrotizing factor 1 and PMA, and reduced by ToxB. caCdc42 also increased endocytotic activity of DC, whereas dominant-negative Cdc42 blocked it. Thus, Rho GTPases Cdc42, RhoA, and Rac1 regulate DC functions that are critical for DC-mediated immune responses in vivo.
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
authors.forename: Galina V
authors.initials: GV
authors.lastname: Shurin
authors.forename: Irina L
authors.initials: IL
authors.lastname: Tourkova
authors.forename: Gurkamal S
authors.initials: GS
authors.lastname: Chatta
authors.forename: Gudula
authors.initials: G
authors.lastname: Schmidt
authors.forename: Sheng
authors.initials: S
authors.lastname: Wei
authors.forename: Julie Y
authors.initials: JY
authors.lastname: Djeu
authors.forename: Michael R
authors.initials: MR
authors.lastname: Shurin
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D002448:Cell Adhesion; D002465:Cell Movement; D002633:Chemotaxis; D003713:Dendritic Cells / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology* / Q000502:physiology; D004705:Endocytosis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014162:Transfection; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000276:immunology; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000276:immunology; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000276:immunology
chemical_list: D004791:Enzyme Inhibitors; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein