The Importance of Alpha-Actinin Proteins in Platelet Formation and Function, and Their Causative Role in Congenital Macrothrombocytopenia
| Autor: | Paul Young, Leanne R O'Sullivan, Mary R. Cahill |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Blood Platelets
Integrins actin cytoskeleton Platelet maturation QH301-705.5 Actinin macromolecular substances Review Biology ACTN1 Catalysis congenital macrothrombocytopenia Inorganic Chemistry Platelet Adhesiveness megakaryocytes macrothrombocytopenia Humans Platelet Platelet activation Physical and Theoretical Chemistry Biology (General) Molecular Biology QD1-999 Spectroscopy Actin CMTP actinin actinin-1 Organic Chemistry General Medicine Actin cytoskeleton Thrombocytopenia Computer Science Applications Cell biology actinin-4 Actinin alpha 1 Chemistry Mutation platelets Function (biology) |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 9363, p 9363 (2021) |
| ISSN: | 1422-0067 |
| Popis: | The actin cytoskeleton plays a central role in platelet formation and function. Alpha-actinins (actinins) are actin filament crosslinking proteins that are prominently expressed in platelets and have been studied in relation to their role in platelet activation since the 1970s. However, within the past decade, several groups have described mutations in ACTN1/actinin-1 that cause congenital macrothrombocytopenia (CMTP)—accounting for approximately 5% of all cases of this condition. These findings are suggestive of potentially novel functions for actinins in platelet formation from megakaryocytes in the bone marrow and/or platelet maturation in circulation. Here, we review some recent insights into the well-known functions of actinins in platelet activation before considering possible roles for actinins in platelet formation that could explain their association with CMTP. We describe what is known about the consequences of CMTP-linked mutations on actinin-1 function at a molecular and cellular level and speculate how these changes might lead to the alterations in platelet count and morphology observed in CMTP patients. Finally, we outline some unanswered questions in this area and how they might be addressed in future studies. |
| Databáze: | OpenAIRE |
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