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Molecular and Cellular Biology, June 2008, p. 3776-3789, Vol. 28, No. 11
0270-7306/08/$08.00+0     doi:10.1128/MCB.00507-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

{alpha}PIX Rho GTPase Guanine Nucleotide Exchange Factor Regulates Lymphocyte Functions and Antigen Receptor Signaling{triangledown}

Karine Missy,1,{dagger} Bin Hu,1,{dagger} Kerstin Schilling,1,2 Anke Harenberg,1 Vadim Sakk,1 Kerstin Kuchenbecker,3 Kerstin Kutsche,3 and Klaus-Dieter Fischer2*

Institute of Physiological Chemistry, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany,1 Institute of Biochemistry and Cell Biology, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany,2 Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Butenfeld 42, 22529 Hamburg, Germany3

Received 22 March 2007/ Returned for modification 30 April 2007/ Accepted 17 March 2008

{alpha}PIX is a Rho GTPase guanine nucleotide exchange factor domain-containing signaling protein that associates with other proteins involved in cytoskeletal-membrane complexes. It has been shown that PIX proteins play roles in some immune cells, including neutrophils and T cells. In this study, we report the immune system phenotype of {alpha}PIX knockout mice. We extended {alpha}PIX expression experiments and found that whereas {alpha}PIX was specific to immune cells, its homolog βPIX was expressed in a wider range of cells. Mice lacking {alpha}PIX had reduced numbers of mature lymphocytes and defective immune responses. Antigen receptor-directed proliferation of {alpha}PIX– T and B cells was also reduced, but basal migration was enhanced. Accompanying these defects, formation of T-cell-B-cell conjugates and recruitment of PAK and Lfa-1 integrin to the immune synapse were impaired in the absence of {alpha}PIX. Proximal antigen receptor signaling was largely unaffected, with the exception of reduced phosphorylation of PAK and expression of GIT2 in both T cells and B cells. These results reveal specific roles for {alpha}PIX in the immune system and suggest that redundancy with βPIX precludes a more severe immune phenotype.

* Corresponding author. Mailing address: Institute of Biochemistry, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany. Phone: 49-391-671-4288. Fax: 49-391-671-5898. E-mail: klaus.fischer{at}med.ovgu.de

{triangledown} Published ahead of print on 31 March 2008.

{dagger} K.M. and B.H. contributed equally to this work.

Molecular and Cellular Biology, June 2008, p. 3776-3789, Vol. 28, No. 11
0270-7306/08/$08.00+0     doi:10.1128/MCB.00507-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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