| First Author | Quast T | Year | 2009 |
| Journal | Blood | Volume | 113 |
| Issue | 23 | Pages | 5801-10 |
| PubMed ID | 19346499 | Mgi Jnum | J:149500 |
| Mgi Id | MGI:3848606 | Doi | 10.1182/blood-2008-08-176123 |
| Citation | Quast T, et al. (2009) Cytohesin-1 controls the activation of RhoA and modulates integrin-dependent adhesion and migration of dendritic cells. Blood 113(23):5801-10 |
| abstractText | 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. |
