Wiskott-Aldrich syndrome protein is involved in alphaIIb beta3-mediated cell adhesion.
The Wiskott-Aldrich syndrome (WAS) is an X-chromosome-linked immunodeficiency disorder. The most common symptom seen in WAS patients is bleeding. One of the main causes of bleeding is defective platelet aggregation. The causative gene of WAS encodes WAS protein (WASP). Here, we show that WASP binds to the calcium- and integrin-binding protein (CIB) in platelets. CIB was originally identified as a protein binding to the alphaIIb cytoplasmic tail of platelet integrin alphaIIb beta3, which has a primary role in platelet aggregation. We also show that the WASP-CIB complex is important in alphaIIb beta3-mediated cell adhesion, and that in patients mutant forms of WASP are expressed at reduced levels or show lower affinities for CIB than wild-type WASP. Our results indicate that impaired complex formation between mutant WASPs and CIB reduces alphaIIb beta3-mediated cell adhesion and causes defective platelet aggregation, resulting in bleeding.
Tsuboi
Shigeru
S
Infectious and Inflammatory Disease Research Center, Burnham Institute for Biomedical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
Nonoyama
Shigeaki
S
Ochs
Hans D
HD
D001792:Blood Platelets / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000097:blood; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D006801:Humans; D009154:Mutation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D014923:Wiskott-Aldrich Syndrome / Q000097:blood / Q000235:genetics; D051316:Wiskott-Aldrich Syndrome Protein / Q000097:blood / Q000502:physiology*
C109198:CIB1 protein, human; D002135:Calcium-Binding Proteins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D051316:Wiskott-Aldrich Syndrome Protein