Integrin regulation by RhoA in thymocytes.
The guanine nucleotide-binding protein Rho has essential functions in T cell development and is important for the survival and proliferation of T cell progenitors in the thymus. To explore the mechanisms used by RhoA to control thymocyte biology, the role of this GTPase in the regulation of integrin-mediated cell adhesion was examined. The data show that RhoA activation is sufficient to stimulate beta(1) and beta(2) integrin-mediated adhesion in murine thymocytes. RhoA is also needed for integrin activation in vivo as loss of Rho function impaired the ability of thymocytes to adhere to the extracellular matrix protein VCAM-1 and prevented integrin activation induced by the GTPases Rac-1 and Rap1A in vivo. The regulated activity of integrins is needed for cell motility and in the present study it was seen that RhoA activity is critical for integrin-mediated thymocyte migration to chemokines in vitro. Thus, RhoA has a critical role in regulating cell adhesion and migration during T cell development.
Lymphocyte Activation Laboratory, Cancer Research U.K. London Research Institute, Lincoln's Inn Fields Laboratories, London, United Kingdom.
Susina
S
Vielkind
Maighread
M
Gallagher-Gambarelli
Manuel
M
Gomez
Heather J
HJ
Hinton
Doreen A
DA
Cantrell
D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology / Q000502:physiology; D002465:Cell Movement; D002634:Chemotaxis, Leukocyte / Q000276:immunology / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D019012:Integrin beta1 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D018821:CD18 Antigens; D019012:Integrin beta1; D016023:Integrins; D019010:Vascular Cell Adhesion Molecule-1; D020830:rac1 GTP-Binding Protein; D020827:rap1 GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein