dc.contributor.author	O'Sullivan, Leanne Rose
dc.contributor.author	Ajaykumar, Praburam Amarendra
dc.contributor.author	Dembicka, Kornelia Maria
dc.contributor.author	Murphy, Aidan
dc.contributor.author	Grennan, Eamonn Paul
dc.contributor.author	Young, Paul W.
dc.contributor.funder	Irish Research Council	en
dc.contributor.funder	University College Cork	en
dc.date.accessioned	2019-09-10T10:11:32Z
dc.date.available	2019-09-10T10:11:32Z
dc.date.issued	2019-07-31
dc.date.updated	2019-08-09T08:36:44Z
dc.description.abstract	Actinin‐1 mutations cause dominantly inherited congenital macrothrombocytopenia (CMTP), with mutations in the actin‐binding domain increasing actinin's affinity for F‐actin. In this study, we examined nine CMTP‐causing mutations in the calmodulin‐like and rod domains of actinin‐1. These mutations increase, to varying degrees, actinin's ability to bundle actin filaments in vitro. Mutations within the calmodulin‐like domain decrease its thermal stability slightly but do not dramatically affect calcium binding, with mutant proteins retaining calcium‐dependent regulation of filament bundling in vitro. The G764S and E769K mutations increase cytoskeletal association of actinin in cells, and all mutant proteins colocalize with F‐actin in cultured HeLa cells. Thus, CMTP‐causing actinin‐1 mutations outside the actin‐binding domain also increase actin association, suggesting a common molecular mechanism underlying actinin‐1 related CMTP.	en
dc.description.sponsorship	Irish Research Council (Government of Ireland Postgraduate Scholarship: Project ID:GOIPG/2017/952); University College Cork (Translational Research Access Programme)	en
dc.description.status	Peer reviewed	en
dc.description.version	Accepted Version	en
dc.format.mimetype	application/pdf	en
dc.identifier.citation	O'Sullivan, L. R., Ajaykumar, P. A., Dembicka, K. M., Murphy, A., Grennan, E. P. and Young, P. W. (2019) 'Investigation of calmodulin‐like and rod domain mutations suggests common molecular mechanism for α‐actinin‐1‐linked congenital macrothrombocytopenia', FEBS Letters. doi: 10.1002/1873-3468.13562	en
dc.identifier.doi	10.1002/1873-3468.13562	en
dc.identifier.eissn	1873-3468
dc.identifier.endpage	14	en
dc.identifier.issn	0014-5793
dc.identifier.journaltitle	FEBS Letters	en
dc.identifier.startpage	1	en
dc.identifier.uri	https://hdl.handle.net/10468/8505
dc.language.iso	en	en
dc.publisher	John Wiley & Sons, Inc.	en
dc.relation.uri	https://febs.onlinelibrary.wiley.com/doi/abs/10.1002/1873-3468.13562
dc.rights	© 2019, Federation of European Biochemical Societies. Published by John Wiley & Sons, Inc. This is the peer reviewed version of the following article: O'Sullivan, L. R., Ajaykumar, P. A., Dembicka, K. M., Murphy, A., Grennan, E. P. and Young, P. W. (2019) 'Investigation of calmodulin‐like and rod domain mutations suggests common molecular mechanism for α‐actinin‐1‐linked congenital macrothrombocytopenia', FEBS Letters. doi: 10.1002/1873-3468.13562, which has been published in final form at https://doi.org/10.1002/1873-3468.13562. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.	en
dc.subject	ACTN1	en
dc.subject	Macrothrombocytopenia	en
dc.subject	Congenital macrothrombocytopenia	en
dc.subject	Actinin‐1	en
dc.subject	Alpha‐actinin	en
dc.subject	α‐actinin	en
dc.title	Investigation of calmodulin‐like and rod domain mutations suggests common molecular mechanism for α‐actinin‐1‐linked congenital macrothrombocytopenia	en
dc.type	Article (peer-reviewed)	en

Investigation of calmodulin‐like and rod domain mutations suggests common molecular mechanism for α‐actinin‐1‐linked congenital macrothrombocytopenia

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