2021 Fiscal Year Final Research Report
Molecular mechanisms of ACTN1-macrothrombocytopenia
| Project/Area Number |
18K07809
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
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| Research Institution | Gihu University of Medical Science |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Keywords | 先天性血小板減少症 |
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| Outline of Final Research Achievements |
In vitro expression analysis of the novel seven ACTN1 variants identified in the genetic analysis of inherited macrothrombocytopenia was performed in CHO cells. Cells transfected with all of the ACTN1 variants showed abnormal formation of filopodia and lamellipodia and induced actin network disorganization and increased thickness of actin fibers. The rod domain variants may cause strong antiparallel dimerization of actinin-1 and result in the abnormal reorganization of platelet cytoskeleton.
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| Free Research Field |
血栓止血学
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| Academic Significance and Societal Importance of the Research Achievements |
先天性巨大血小板症の原因となるACTN1異常症の遺伝子異常の多くはアクチン結合部位およびカルモジュリン結合部位に同定されていたが、アクチニン二量体形成に関わるスペーサー領域異常はアクチニンの逆平行配位形成を強固にすることでFアクチンの異常構成に関連することが明らかとなった。
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