AlphaPIX Rho GTPase guanine nucleotide exchange factor regulates lymphocyte functions and antigen receptor signaling.
AlphaPIX 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 alphaPIX knockout mice. We extended alphaPIX expression experiments and found that whereas alphaPIX was specific to immune cells, its homolog betaPIX was expressed in a wider range of cells. Mice lacking alphaPIX had reduced numbers of mature lymphocytes and defective immune responses. Antigen receptor-directed proliferation of alphaPIX(-) 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 alphaPIX. 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 alphaPIX in the immune system and suggest that redundancy with betaPIX precludes a more severe immune phenotype.
Missy
Karine
K
Institute of Physiological Chemistry, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
Hu
Bin
B
Schilling
Kerstin
K
Harenberg
Anke
A
Sakk
Vadim
V
Kuchenbecker
Kerstin
K
Kutsche
Kerstin
K
Fischer
Klaus-Dieter
KD
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002465:Cell Movement / Q000235:genetics; D005260:Female; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000819:agonists / Q000378:metabolism*; D064067:Rho Guanine Nucleotide Exchange Factors; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
C576607:Arhgef7 protein, mouse; D018797:Cell Cycle Proteins; D020690:GTPase-Activating Proteins; C120767:Git2 protein, mouse; D020662:Guanine Nucleotide Exchange Factors; D036341:Intercellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell; D064067:Rho Guanine Nucleotide Exchange Factors