title: Cortactin regulates the activity of small GTPases and ICAM-1 clustering in endothelium: Implications for the formation of docking structures.
abstract: Cortactin is an actin-binding molecule that regulates various cellular processes requiring actin dynamics. We recently described cortactin-deficient mice and despite its pivotal role for actin remodeling in vitro, these mice are surprisingly healthy. Analyzing cortactin functions in endothelium under inflammatory conditions, we found that cortactin is required for endothelial barrier functions and leukocyte extravasation in vivo. Importantly, these effects were not regulated by defective actin dynamics but instead by a failure to activate the small GTPases Rap1 and RhoG in endothelial cells. Defective RhoG signaling led to reduced ICAM-1 clustering that supported the interaction with leukocytes. These clusters originally seen as rings surrounding adherent leukocytes actually represented in many cases ICAM-1 containing protrusions as they were described before as docking structures. Thus, cortactin is essential for the formation of endothelial docking structures as well as for leukocyte adhesion and extravasation.
authors.affiliation: Department for Vascular Cell Biology; Max-Planck-Institute for Molecular Biomedicine; Münster, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Vestweber
authors.affiliation: Department for Vascular Cell Biology; Max-Planck-Institute for Molecular Biomedicine; Münster, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Zeuschner
authors.affiliation: Actin Dynamics and Motility Unit; Institute of Genetics; University of Bonn; Bonn, Germany ; Helmholtz Centre for Infection Research; Braunschweig, Germany.
authors.forename: Klemens
authors.initials: K
authors.lastname: Rottner
authors.affiliation: Department for Molecular Biomedicine; CINVESTAV; Mexico City, Mexico.
authors.forename: Michael
authors.initials: M
authors.lastname: Schnoor
keywords: ICAM-1; Rap1; RhoG; actin; docking structure; leukocyte extravasation; transmigratory cup; vascular permeability