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

Quast T, Tappertzhofen B, Schild C, Grell J, Czeloth N, Förster R, Alon R, Fraemohs L, Dreck K, Weber C, Lämmermann T, Sixt MK, Kolanus W. 2009. Cytohesin-1 controls the activation of RhoA and modulates integrin-dependent adhesion and migration of dendritic cells. Blood. 113(23), 5801–5810.

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Author
Quast, Thomas; Tappertzhofen, Barbara; Schild, Cora; Grell, Jessica; Czeloth, Niklas; Förster, Reinhold; Alon, Ronen; Fraemohs, Line; Dreck, Katrin; Weber, Christian; Lämmermann, Tim; Sixt, Michael KIST Austria
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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.
Publishing Year
Date Published
2009-06-04
Journal Title
Blood
Volume
113
Issue
23
Page
5801 - 5810
IST-REx-ID

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Quast T, Tappertzhofen B, Schild C, et al. Cytohesin-1 controls the activation of RhoA and modulates integrin-dependent adhesion and migration of dendritic cells. Blood. 2009;113(23):5801-5810. doi:10.1182/blood-2008-08-176123
Quast, T., Tappertzhofen, B., Schild, C., Grell, J., Czeloth, N., Förster, R., … Kolanus, W. (2009). Cytohesin-1 controls the activation of RhoA and modulates integrin-dependent adhesion and migration of dendritic cells. Blood. American Society of Hematology. https://doi.org/10.1182/blood-2008-08-176123
Quast, Thomas, Barbara Tappertzhofen, Cora Schild, Jessica Grell, Niklas Czeloth, Reinhold Förster, Ronen Alon, et al. “Cytohesin-1 Controls the Activation of RhoA and Modulates Integrin-Dependent Adhesion and Migration of Dendritic Cells.” Blood. American Society of Hematology, 2009. https://doi.org/10.1182/blood-2008-08-176123.
T. Quast et al., “Cytohesin-1 controls the activation of RhoA and modulates integrin-dependent adhesion and migration of dendritic cells,” Blood, vol. 113, no. 23. American Society of Hematology, pp. 5801–5810, 2009.
Quast T, Tappertzhofen B, Schild C, Grell J, Czeloth N, Förster R, Alon R, Fraemohs L, Dreck K, Weber C, Lämmermann T, Sixt MK, Kolanus W. 2009. Cytohesin-1 controls the activation of RhoA and modulates integrin-dependent adhesion and migration of dendritic cells. Blood. 113(23), 5801–5810.
Quast, Thomas, et al. “Cytohesin-1 Controls the Activation of RhoA and Modulates Integrin-Dependent Adhesion and Migration of Dendritic Cells.” Blood, vol. 113, no. 23, American Society of Hematology, 2009, pp. 5801–10, doi:10.1182/blood-2008-08-176123.

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