title: The adaptor protein Swiprosin-1/EFhd2 is dispensable for platelet function in mice.
abstract: BACKGROUND
  Platelets 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.
  
  
  OBJECTIVE
  Based 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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  These results show that EFhd2 is not essential for platelet function in mice indicating that other cytoskeletal adaptors may functionally compensate its loss.
authors.affiliation: University of Würzburg, Department of Experimental Biomedicine, University Hospital and Rudolf Virchow Center for Experimental Biomedicine, Würzburg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Morowski
authors.affiliation: Division of Molecular Immunology, Department of Internal Medicine III, Nikolaus Fiebiger Center, University Hospital Erlangen and University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brachs
authors.affiliation: Division of Molecular Immunology, Department of Internal Medicine III, Nikolaus Fiebiger Center, University Hospital Erlangen and University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Mielenz
authors.affiliation: University of Würzburg, Department of Experimental Biomedicine, University Hospital and Rudolf Virchow Center for Experimental Biomedicine, Würzburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
authors.affiliation: University of Würzburg, Department of Experimental Biomedicine, University Hospital and Rudolf Virchow Center for Experimental Biomedicine, Würzburg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dütting
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D015539:Platelet Activation / Q000235:genetics*; D010974:Platelet Aggregation / Q000235:genetics*; D010979:Platelet Function Tests
chemical_list: D002135:Calcium-Binding Proteins; C530752:EFHD2 protein, mouse