Palladin is involved in platelet activation and arterial thrombosis

Thromb Res. 2017 Jan;149:1-8. doi: 10.1016/j.thromres.2016.11.010. Epub 2016 Nov 10.

Abstract

The dynamics of actin cytoskeleton have been shown to play a critical role during platelet activation. Palladin is an actin-associated protein, serving as a cytoskeleton scaffold to bundle actin fibers and actin cross linker. The functional role of palladin on platelet activation has not been investigated. Here, we characterized heterozygous palladin knockout (palladin+/-) mice to elucidate the platelet-related functions of palladin. The results showed that palladin was expressed in platelets and moderate palladin deficiency accelerated hemostasis and arterial thrombosis. The aggregation of palladin+/- platelets was increased in response to low levels of thrombin, U46619, and collagen. We also observed enhanced spreading of palladin+/- platelets on immobilized fibrinogen (Fg) and increased rate of clot retraction in platelet-rich plasma (PRP) containing palladin+/- platelets. Furthermore, the activation of the small GTPase Rac1 and Cdc42, which is associated with cytoskeletal dynamics and platelet activation signalings, was increased in the spreading and aggregating palladin+/- platelets compared to that in wild type platelets. Taken together, these findings indicated that palladin is involved in platelet activation and arterial thrombosis, implying a potent role of palladin in pathophysiology of thrombotic diseases.

Keywords: Cdc42; Knockout mice; Paladin; Platelet activation; Rac1.

MeSH terms

  • Animals
  • Blood Platelets / cytology
  • Blood Platelets / metabolism
  • Blood Platelets / pathology*
  • Cytoskeletal Proteins / analysis
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Hemostasis
  • Humans
  • Mice, Knockout
  • Neuropeptides / metabolism
  • Phosphoproteins / analysis
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Platelet Activation*
  • Platelet-Rich Plasma / cytology
  • Platelet-Rich Plasma / metabolism
  • Thrombosis / blood
  • Thrombosis / genetics
  • Thrombosis / metabolism*
  • Thrombosis / pathology*
  • cdc42 GTP-Binding Protein / metabolism
  • rac1 GTP-Binding Protein / metabolism

Substances

  • Cdc42 protein, mouse
  • Cytoskeletal Proteins
  • Neuropeptides
  • Phosphoproteins
  • Rac1 protein, mouse
  • palladin protein, mouse
  • cdc42 GTP-Binding Protein
  • rac1 GTP-Binding Protein