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Molecular and Cellular Biology, January 2006, p. 643-653, Vol. 26, No. 2
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.2.643-653.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Rap1A-Deficient T and B Cells Show Impaired Integrin-Mediated Cell Adhesion

Marlena Duchniewicz,1,2,{dagger} Tomasz Zemojtel,3,4,{dagger}* Mateusz Kolanczyk,5 Steffen Grossmann,3 Jürgen S. Scheele,1,6 and Fried J. T. Zwartkruis7

Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Ihnestrasse 73, D-14195 Berlin, Germany,3 Department of Medicine I,1 Department of Biology I, University of Freiburg Medical Center, D-79106 Freiburg, Germany,2 Department of Development and Disease, Max Planck Institute for Molecular Genetics, Ihnestrasse 73, D-14195 Berlin, Germany,5 In silico Miners, ul. Chopina 13/10, 81-782 Sopot, Poland,4 Department of Pharmacology I and Clinical Trials Center, University of Freiburg Medical Center, D-79104 Freiburg, Germany,6 Department of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG Utrecht The Netherlands7

Received 19 August 2005/ Accepted 24 October 2005

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.

* Corresponding author. Mailing address: Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Ihnestrasse 73, D-14195 Berlin, Germany. Phone: 49-30-8413-1147. Fax: 49-30-8413-1152. E-mail: zemojtel{at}molgen.mpg.de.

{dagger} M.D. and T.Z. contributed equally to this study.

Molecular and Cellular Biology, January 2006, p. 643-653, Vol. 26, No. 2
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.2.643-653.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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