αPIX Rho GTPase guanine nucleotide exchange factor regulates lymphocyte functions and antigen receptor signaling

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 PPIX was expressed in a wider range of cells. Mice lacking aPIX 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 PPIX precludes a more severe immune phenotype.