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

MPG-Autoren
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Lämmermann,  Tim
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Externe Ressourcen

https://ashpublications.org/blood/article/113/23/5801/25888/Cytohesin-1-controls-the-activation-of-RhoA-and
(Verlagsversion)

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Quast et al..pdf
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Zitation

Quast, T., Tappertzhofen, B., Schild, C., Grell, J., Czeloth, N., Förster, R., et al. (2009). Cytohesin-1 controls the activation of RhoA and modulates integrin-dependent adhesion and migration of dendritic cells. Blood, 113, 5801-5810. doi:10.1182/blood-2008-08-176123.


Zitierlink: https://hdl.handle.net/21.11116/0000-0007-73D8-4
Zusammenfassung
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.