Cytohesin-1 controls the activation of RhoA and modulates integrin-dependent adhesion and migration of dendritic cells.
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.
Life and Medical Sciences Institute, Laboratory for Molecular Immunology, University of Bonn, Bonn, Germany.
Thomas
T
Quast
Barbara
B
Tappertzhofen
Cora
C
Schild
Jessica
J
Grell
Niklas
N
Czeloth
Reinhold
R
Förster
Ronen
R
Alon
Line
L
Fraemohs
Katrin
K
Dreck
Christian
C
Weber
Tim
T
Lämmermann
Michael
M
Sixt
Waldemar
W
Kolanus
D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism*; D004789:Enzyme Activation; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D034622:RNA Interference; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D018821:CD18 Antigens; D020662:Guanine Nucleotide Exchange Factors; D016023:Integrins; C100723:cytohesin-1; D020742:rhoA GTP-Binding Protein