| Project/Area Number |
14370243
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
KAJIWARA Michiko Tokyo Medical and Dental University, Department Transfusion Medicine, Research Associate, 医学部附属病院, 助手 (40280979)
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| Co-Investigator(Kenkyū-buntansha) |
ONOYAMA Shigeaki National Defence Medical Collage, Department of Pediatrics, Professor, 小児科, 教授
MINEGISHI Yosiyuki Tokyo Medical and Dental University, Department of Immunology, Associate Professor, 大学院・医歯学総合研究科, 助教授 (10343154)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥13,300,000 (Direct Cost: ¥13,300,000)
Fiscal Year 2003: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 2002: ¥6,900,000 (Direct Cost: ¥6,900,000)
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| Keywords | Wiskott-Aldrich syndrome / WASP / Integrin / Platelets / CIB |
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| Research Abstract |
The Wiskott-Aldrich syndrome (WAS) is an X chromosome-linked immunodeficiency characterized by bleeding, eczema and recurrent infections. The causative gene encodes the WAS protein (WASP) which plays an important role in the assembly of actin cytoskeleton and signal transduction. Although the severity of WAS correlated with the expression level of WASP, bleeding was commonly observed both in severe and mild types of WAS patients, suggesting that the WASP is critical for the platelet function. In this study we analyzed the role of WASP in the platelet aggregation. We found that the WASP N-terminus binds to a calcium-binding protein, calcium-and integrin-binding protein (CIB). CIB was originally reported to bind to the α IIb cytoplasmic tail of platelet integrin α IIb β3 which plays a primary role in platelet aggregation. Blocking of WASP binding to CIB resulted in impaired activation of α IIb β 3. Activation of α IIb β3 is impaired in platelets from WAS patients. Reduced levels of mutant WASP expression and lower affinity of mutant WASP for CIB make formation of the CIB-mutant WASP complex inefficient, resulting in the impaired α IIb β3 activation. These results indicate that WASP is involved in platelet aggregation through association with CIB.
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