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Cytohesin-1 controls the activation of RhoA and modulates integrin-dependent adhesion and migration of dendritic cells. |
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AbstractAdhesion and motility of mammalian leukocytes are essential requirements for innate and adaptive immune defence 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 (DC). Cytohesin-1 and RhoA are both required for the induction of chemokine-dependent conformational changes of the integrin beta-2 subunit of DC during adhesion under physiological flow conditions. Furthermore, employment of RNAi in murine BM-DC revealed that interference with cytohesin-1 signaling impairs migration of wild type dendritic cells in complex 3D environments and in vivo. This phentoype was not observed in the complete absence of integrins. We thus demonstrate an essential role of cytohesin-1/RhoA during amoeboid migration in the presence of integrins and further suggest that DCs without integrins switch to a different migration mode.
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