Novel membrane cell projection defects in Wiskott-Aldrich syndrome B cells.
Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by microthrombocytopenia, eczema, recurrent infections, autoimmune disorders and an increased incidence of malignancies. This complex phenotype results from mutations in the WASP gene. WASP is a key member of a protein family that links signaling pathways to actin cytoskeleton reorganization by activating Arp2/3-mediated actin polymerization. Actin polymerization defects have been extensively defined in WAS T cells and also in dendritic cells and macrophages, but few reports have concentrated on WAS B cells. In the present study, we investigated cytoskeleton abnormalities in WAS B cell lines. For the first time we report alterations in the capacity of these cells to extend filopodia in response to bradykinin stimuli and an impairment in the formation of long pseudopodia under basal conditions. Such alterations most probably result from a WASP dysfunction, given that a retroviral gene transfer of a corrected form of the WASP gene was able to rescue the abnormal phenotypes.
Andreu
Nuria
N
Programa Gens i Malaltia, Centre de Regulació Genòmica-CRG-UPF, Parc de Recerca Biomèdica (PRBB), 08003 Barcelona, Spain.
Aran
Josep M
JM
Fillat
Cristina
C
D000199:Actins / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology*; D001920:Bradykinin / Q000494:pharmacology; D004854:Herpesvirus 4, Human; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010957:Plasmids / Q000378:metabolism; D011554:Pseudopodia / Q000187:drug effects / Q000473:pathology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012190:Retroviridae; D014161:Transduction, Genetic; D014923:Wiskott-Aldrich Syndrome / Q000473:pathology*; D051316:Wiskott-Aldrich Syndrome Protein / Q000378:metabolism