Journal
THROMBOSIS RESEARCH
Volume 149, Issue -, Pages 1-8Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.thromres.2016.11.010
Keywords
Paladin; Knockout mice; Platelet activation; Rac1; Cdc42
Categories
Funding
- National Natural Science Foundation of China [81430028]
- Ministry of Science and Technology of China [2011BAI15B02]
- Science and Technology Commission of Shanghai Municipality [13DZ2280600, 13DZ2293700, 15DZ2290800, 12ZR1421100, 16ZR1423700]
- E-Institutes of Shanghai Municipal Education Commission [E03003]
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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. (C) 2016 Elsevier Ltd. All rights reserved.
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