Abstract
BackgroundPlatelets are anuclear cell fragments derived from bone marrow megakaryocytes that safeguard vascular integrity, but may also cause pathological vessel occlusion. Reorganizations of the platelet cytoskeleton and agonist-induced intracellular Ca2+-mobilization are crucial for platelet hemostatic function. EF-hand domain containing 2 (EFhd2, Swiprosin-1) is a Ca2+-binding cytoskeletal adaptor protein involved in actin remodeling in different cell types, but its function in platelets is unknown.ObjectiveBased on the described functions of EFhd2 in immune cells, we tested the hypothesis that EFhd2 is a crucial adaptor protein for platelet function acting as a regulator of Ca2+-mobilization and cytoskeletal rearrangements.Methods and ResultsWe generated EFhd2-deficient mice and analyzed their platelets in vitro and in vivo. Efhd2-/- mice displayed normal platelet count and size, exhibited an unaltered in vivo life span and showed normal Ca2+-mobilization and activation/aggregation responses to classic agonists. Interestingly, upon stimulation of the immunoreceptor tyrosine-based activation motif-coupled receptor glycoprotein (GP) VI, Efhd2-/- platelets showed a slightly increased coagulant activity. Furthermore, absence of EFhd2 had no significant impact on integrin-mediated clot retraction, actomyosin rearrangements and spreading of activated platelets on fibrinogen. In vivo EFhd2-deficiency resulted in unaltered hemostatic function and unaffected arterial thrombus formation.ConclusionThese results show that EFhd2 is not essential for platelet function in mice indicating that other cytoskeletal adaptors may functionally compensate its loss.
Highlights
Platelets are small anucleated cell fragments derived from the cytoplasm of bone marrow megakaryocytes (MKs)
In vivo EFhd2-deficiency resulted in unaltered hemostatic function and unaffected arterial thrombus formation
At sites of vascular injury, platelets adhere and aggregate on the exposed subendothelial extracellular matrix (ECM) and thereby form a plug that seals the wound. This process is essential for normal hemostasis, but in diseased vessels it may lead to pathological thrombus formation and infarction of vital organs [1,2]
Summary
Platelets are small anucleated cell fragments derived from the cytoplasm of bone marrow megakaryocytes (MKs). Platelet activation on the injured vessel wall is induced by multiple signaling pathways and leads to extensive cytoskeletal rearrangements that are crucial for conversion from discoid to spheric shape, granule secretion, spreading and, at later time points clot retraction [3]. Many of these processes are controlled by proteins of the Rho family of small GTPases, like RhoA, Rac, and Cdc and their downstream effector molecules such as the WiskottAldrich syndrome proteins (WASPs), formins and p21-activated kinases (PAKs) [4]. EF-hand domain containing 2 (EFhd, Swiprosin-1) is a Ca2+-binding cytoskeletal adaptor protein involved in actin remodeling in different cell types, but its function in platelets is unknown
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