Cytohesin-1 controls the activation of RhoA and modulates integrin-dependent adhesion and migration of dendritic cells Journal Article


Author(s): Quast, Thomas; Tappertzhofen, Barbara; Schild, Cora; Grell, Jessica; Czeloth, Niklas; Förster, Reinhold; Alon, Ronen; Fraemohs, Line; Dreck, Katrin; Weber, Christian; Lämmermann, Tim; Sixt, Michael; Kolanus, Waldemar
Article Title: Cytohesin-1 controls the activation of RhoA and modulates integrin-dependent adhesion and migration of dendritic cells
Affiliation
Abstract: Adhesion and motility of mammalian leukocytes are essential requirements for innate and adaptive immune defense mechanisms. We show here that the guanine nucleotide exchange factor cytohesin-1, which had previously been demonstrated to be an important component of beta-2 integrin activation in lymphocytes, regulates the activation of the small GTPase RhoA in primary dendritic cells (DCs). Cytohesin-1 and RhoA are both required for the induction of chemokine-dependent conformational changes of the integrin beta-2 subunit of DCs during adhesion under physiological flow conditions. Furthermore, use of RNAi in murine bone marrow DCs (BM-DCs) revealed that interference with cytohesin-1 signaling impairs migration of wild-type dendritic cells in complex 3D environments and in vivo. This phenotype was not observed in the complete absence of integrins. We thus demonstrate an essential role of cytohesin-1/RhoA during ameboid migration in the presence of integrins and further suggest that DCs without integrins switch to a different migration mode.
Keywords: Animals; Humans; Cells, Cultured; Mice; *Cell Movement; RNA Interference; Cell Adhesion; Antigens, CD18/metabolism; Cell Differentiation; Dendritic Cells/*cytology/*metabolism; Enzyme Activation; Guanine Nucleotide Exchange Factors/*metabolism; Integrins/*metabolism; rhoA GTP-Binding Protein/*metabolism
Journal Title: Blood
Volume: 113
Issue 23
ISSN: 1528-0020
Publisher: American Society of Hematology  
Publication Place: United States
Date Published: 2009-06-04
Start Page: 5801
End Page: 5810
DOI: 10.1182/blood-2008-08-176123
Open access: no