The cytoskeletal crosslinking protein MACF1 is dispensable for thrombus formation and hemostasis

Abstract Coordinated reorganization of cytoskeletal structures is critical for key aspects of platelet physiology. While several studies have addressed the role of microtubules and filamentous actin in platelet production and function, the significance of their crosstalk in these processes has been...

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Main Authors: Yvonne Schurr, Markus Spindler, Hendrikje Kurz, Markus Bender
Format: Article
Language:English
Published: Nature Publishing Group 2019-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-019-44183-6
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spelling doaj-c264abe5737d4c679b3a80504f711f3b2020-12-08T07:34:19ZengNature Publishing GroupScientific Reports2045-23222019-05-01911810.1038/s41598-019-44183-6The cytoskeletal crosslinking protein MACF1 is dispensable for thrombus formation and hemostasisYvonne Schurr0Markus Spindler1Hendrikje Kurz2Markus Bender3Institute of Experimental Biomedicine – Chair I, University Hospital and Rudolf Virchow CenterInstitute of Experimental Biomedicine – Chair I, University Hospital and Rudolf Virchow CenterInstitute of Experimental Biomedicine – Chair I, University Hospital and Rudolf Virchow CenterInstitute of Experimental Biomedicine – Chair I, University Hospital and Rudolf Virchow CenterAbstract Coordinated reorganization of cytoskeletal structures is critical for key aspects of platelet physiology. While several studies have addressed the role of microtubules and filamentous actin in platelet production and function, the significance of their crosstalk in these processes has been poorly investigated. The microtubule-actin cross-linking factor 1 (MACF1; synonym: Actin cross-linking factor 7, ACF7) is a member of the spectraplakin family, and one of the few proteins expressed in platelets, which possess actin and microtubule binding domains thereby facilitating actin-microtubule interaction and regulation. We used megakaryocyte- and platelet-specific Macf1 knockout (Macf1 fl/fl , Pf4-Cre) mice to study the role of MACF1 in platelet production and function. MACF1 deficient mice displayed comparable platelet counts to control mice. Analysis of the platelet cytoskeletal ultrastructure revealed a normal marginal band and actin network. Platelet spreading on fibrinogen was slightly delayed but platelet activation and clot traction was unaffected. Ex vivo thrombus formation and mouse tail bleeding responses were similar between control and mutant mice. These results suggest that MACF1 is dispensable for thrombopoiesis, platelet activation, thrombus formation and the hemostatic function in mice.https://doi.org/10.1038/s41598-019-44183-6
collection DOAJ
language English
format Article
sources DOAJ
author Yvonne Schurr
Markus Spindler
Hendrikje Kurz
Markus Bender
spellingShingle Yvonne Schurr
Markus Spindler
Hendrikje Kurz
Markus Bender
The cytoskeletal crosslinking protein MACF1 is dispensable for thrombus formation and hemostasis
Scientific Reports
author_facet Yvonne Schurr
Markus Spindler
Hendrikje Kurz
Markus Bender
author_sort Yvonne Schurr
title The cytoskeletal crosslinking protein MACF1 is dispensable for thrombus formation and hemostasis
title_short The cytoskeletal crosslinking protein MACF1 is dispensable for thrombus formation and hemostasis
title_full The cytoskeletal crosslinking protein MACF1 is dispensable for thrombus formation and hemostasis
title_fullStr The cytoskeletal crosslinking protein MACF1 is dispensable for thrombus formation and hemostasis
title_full_unstemmed The cytoskeletal crosslinking protein MACF1 is dispensable for thrombus formation and hemostasis
title_sort cytoskeletal crosslinking protein macf1 is dispensable for thrombus formation and hemostasis
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2019-05-01
description Abstract Coordinated reorganization of cytoskeletal structures is critical for key aspects of platelet physiology. While several studies have addressed the role of microtubules and filamentous actin in platelet production and function, the significance of their crosstalk in these processes has been poorly investigated. The microtubule-actin cross-linking factor 1 (MACF1; synonym: Actin cross-linking factor 7, ACF7) is a member of the spectraplakin family, and one of the few proteins expressed in platelets, which possess actin and microtubule binding domains thereby facilitating actin-microtubule interaction and regulation. We used megakaryocyte- and platelet-specific Macf1 knockout (Macf1 fl/fl , Pf4-Cre) mice to study the role of MACF1 in platelet production and function. MACF1 deficient mice displayed comparable platelet counts to control mice. Analysis of the platelet cytoskeletal ultrastructure revealed a normal marginal band and actin network. Platelet spreading on fibrinogen was slightly delayed but platelet activation and clot traction was unaffected. Ex vivo thrombus formation and mouse tail bleeding responses were similar between control and mutant mice. These results suggest that MACF1 is dispensable for thrombopoiesis, platelet activation, thrombus formation and the hemostatic function in mice.
url https://doi.org/10.1038/s41598-019-44183-6
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