Rap1A-deficient T and B cells show impaired integrin-mediated cell adhesion.
Studies in tissue culture cells have demonstrated a role for the Ras-like GTPase Rap1 in the regulation of integrin-mediated cell-matrix and cadherin-mediated cell-cell contacts. To analyze the function of Rap1 in vivo, we have disrupted the Rap1A gene by homologous recombination. Mice homozygous for the deletion allele are viable and fertile. However, primary hematopoietic cells isolated from spleen or thymus have a diminished adhesive capacity on ICAM and fibronectin substrates. In addition, polarization of T cells from Rap1-/- cells after CD3 stimulation was impaired compared to that of wild-type cells. Despite this, these defects did not result in hematopoietic or cell homing abnormalities. Although it is possible that the relatively mild phenotype is a consequence of functional complementation by the Rap1B gene, our genetic studies confirm a role for Rap1A in the regulation of integrins.
Duchniewicz
Marlena
M
Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Ihnestrasse 73, D-14195 Berlin, Germany.
Zemojtel
Tomasz
T
Kolanczyk
Mateusz
M
Grossmann
Steffen
S
Scheele
Jürgen S
JS
Zwartkruis
Fried J T
FJ
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D017252:CD3 Complex / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D049109:Cell Proliferation; D004622:Embryo, Mammalian / Q000166:cytology; D005353:Fibronectins / Q000378:metabolism; D006410:Hematopoiesis; D066298:In Vitro Techniques; D039041:Integrin alpha4beta1 / Q000502:physiology; D016023:Integrins / Q000502:physiology*; D008198:Lymph Nodes / Q000166:cytology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism; D020827:rap1 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D020827:rap1 GTP-Binding Proteins