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 (Macf1fl/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.
Highlights
Platelets are anucleated cell fragments derived from megakaryocytes (MKs) in the bone marrow
Due to embryonic lethality of constitutive Microtubule-actin cross-linking factor 1 (MACF1) deficient mice on day 11.5 (E11.5)[21], we capitalized on MK-/platelet-specific knockout mice (Macf1fl/fl, platelet factor 4 (Pf4)-Cre further referred to as Macf1−/−) and the respective littermate controls (Macf1fl/fl further referred to as Macf1+/+)
Shape and ultrastructure were unaltered in Macf1−/− mice, as confirmed by flow cytometry (Fig. 1C) and transmission electron microscopy (TEM) (Fig. 1E), respectively
Summary
Platelets are anucleated cell fragments derived from megakaryocytes (MKs) in the bone marrow. MACF1 was described as an essential integrator of actin-dependent microtubule dynamics[18], and a study in mouse keratinocytes revealed that MACF1 deficiency compromises the targeting of microtubules along F-actin to focal adhesions[19]. For axon extension and the organization of neuronal microtubules, a function dependent on both the microtubule and F-actin-binding domains[20]. These data demonstrate that the crosstalk between cytoskeletal components is essential for the orchestration of basic cellular functions. This crosstalk, has only been poorly studied in platelet biology, and the role of MACF1 in MKs and platelets is unknown. We used MK- and platelet-specific knockout mice to investigate the function of MACF1 in platelet formation, in vitro platelet activation as well as aggregation
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