Thromb Haemost 2018; 118(12): 2098-2111
DOI: 10.1055/s-0038-1675604
Cellular Haemostasis and Platelets
Georg Thieme Verlag KG Stuttgart · New York

The Actin Regulator Coronin-1A Modulates Platelet Shape Change and Consolidates Arterial Thrombosis

Thomas J. Stocker*
1  Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany
2  DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
,
Joachim Pircher*
1  Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany
2  DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
,
Artid Skenderi
1  Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany
,
Andreas Ehrlich
1  Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany
,
Clemens Eberle
1  Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany
,
Remco T. A. Megens
3  Institute for the Prevention of Cardiovascular Diseases (IPEK), Ludwig-Maximilians-Universität München, Munich, Germany
4  Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
,
Tobias Petzold
1  Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany
2  DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
,
Zhe Zhang
1  Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany
,
Barbara Walzog
5  Walter Brendel Centre of Experimental Medicine, Department of Cardiovascular Physiology and Pathophysiology, Biomedical Center, Ludwig-Maximilians-Universität, Planegg-Martinsried, Germany
,
Annette Müller-Taubenberger
6  Department of Cell Biology (Anatomy III), Biomedical Center, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany
,
Christian Weber
2  DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
3  Institute for the Prevention of Cardiovascular Diseases (IPEK), Ludwig-Maximilians-Universität München, Munich, Germany
7  Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
,
Steffen Massberg
1  Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany
2  DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
,
Hellen Ishikawa-Ankerhold*
1  Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany
,
Christian Schulz*
1  Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany
2  DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
› Author Affiliations
Funding Our studies were supported by the SFB914, projects A02 (to B.W.), A07 (to A.M.), A10 (to C.S.) and Z01 (to S.M.), the SFB1123, projects A01 (to C.W.), B06 (to. S.M.) and Z01 (to R.M.), INST 409/150-1 FUGG (to C.W., R.M.), the DZHK (German Centre for Cardiovascular Research), the BMBF (German Ministry of Education and Research) (to S.M.) and the Friedrich-Baur-Stiftung (to J. P.). T.J.S. is supported by Förderprogramm für Forschung und Lehre (FöFoLe) of LMU and in the initial phase of the project by Verein zur Förderung von Wissenschaft und Forschung an der Medizinischen Fakultät der LMU. J.P. is supported by a Gerok position of the SFB914.
Further Information

Publication History

25 March 2018

22 September 2018

Publication Date:
19 November 2018 (eFirst)

Abstract

Coronin-1A (Coro1A) belongs to a family of highly conserved actin-binding proteins that regulate cytoskeletal re-arrangement. In mammalians, Coro1A expression is most abundant in the haematopoietic lineage, where it regulates various cellular processes. The role of Coro1A in platelets has been previously unknown. Here, we identified Coro1A in human and mouse platelets. Genetic absence of Coro1A in mouse platelets inhibited agonist-induced actin polymerization and altered cofilin phosphoregulation, leading to a reduction in spreading and low-dose collagen induced aggregation. Furthermore, Coro1A-deficient mice displayed a defect in ferric chloride-induced arterial thrombosis with prolonged thrombus formation and reduced thrombus size. Immunofluorescence analysis revealed a less compact thrombus structure with reduced density of platelets and fibrinogen. In summary, Coro1A has a role in platelet biology with impact on spreading, aggregation and thrombosis.

* These authors contributed equally to the study.


Supplementary Material