Abstract
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.
Highlights
Disorders of platelet number of unknown cause are increasingly diagnosed in the haematology laboratory during routine blood counts [1], which may go without further investigation if not associated with bleeding [2], but these findings raise questions about genetic influences on platelet count
Actinins are major actin crosslinking proteins in platelets that have recently been linked in genetic studies to abnormalities in platelet count and size [4]—joining other cytoskeletal proteins including myosins (MYH9), fimbrin and tubulin subunits in this regard [5]
Our objective here is to review what is known about the roles of actinins in platelet generation and function, and outline potential cellular and molecular mechanisms that may underlie the platelet abnormalities associated with actinin-1 mutations
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Our objective here is to review what is known about the roles of actinins in platelet generation and function, and outline potential cellular and molecular mechanisms that may underlie the platelet abnormalities associated with actinin-1 mutations. We will outline the key moof 14 lecular interactions of actinins with integrins and other platelet proteins. Turning to the genetic variations within the actinin-1 gene that cause macrothrombocytopenia (CMTP), we will focus on the cellular and molecular consequences of these mutations and specumolecular interactions of in actinins with integrinsand andfunction other platelet proteins. Genetic variations within theopen actinin-1 genethat that need causetomacrothrombocytopenia (CMTP), we will outline some of the questions be addressed by future research we will focus on the cellular and molecular consequences of these mutations and speculate in this area. F-actin binding and crosslinking proteins that are part
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
