Paxillin is an intrinsic negative regulator of platelet activation in mice

Thrombosis Journal

Yoichi Sakata¹  Kazuomi Kario⁴  Jun Mimuro¹  Seiji Madoiwa¹  Hidenori Suzuki³  Satoshi Nishimura²  Tsukasa Ohmori¹  Asuka Sakata⁴ 

[1] Research Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University School of Medicine, 3111-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan;Translational Systems Biology and Medicine Initiative, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan;Department of Morphological and Biomolecular Research, Nippon Medical School, 1-1-5 Sendagi, Bunkyo, Tokyo 113-8602, Japan;Division of Cardiovascular Medicine, Department of Internal Medicine, Jichi Medical University School of Medicine, 3111-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan

关键词: Release reaction;    Platelet aggregation;    Glycoprotein;    Platelet;   

Others  :  834750
DOI  :  10.1186/1477-9560-12-1

 received in 2013-11-26, accepted in 2013-12-09,  发布年份 2014

【 摘 要 】

Background

Paxillin is a LIM domain protein localized at integrin-mediated focal adhesions. Although paxillin is thought to modulate the functions of integrins, little is known about the contribution of paxillin to signaling pathways in platelets. Here, we studied the role of paxillin in platelet activation in vitro and in vivo.

Methods and results

We generated paxillin knockdown (Pxn-KD) platelets in mice by transplanting bone marrow cells transduced with a lentiviral vector carrying a short hairpin RNA sequence, and confirmed that paxillin expression was significantly reduced in platelets derived from the transduced cells. Pxn-KD platelets showed a slight increased in size and augmented integrin αIIbβ3 activation following stimulation of multiple receptors including glycoprotein VI and G protein-coupled receptors. Thromboxane A₂ biosynthesis and the release of α-granules and dense granules in response to agonist stimulation were also enhanced in Pxn-KD platelets. However, Pxn-KD did not increase tyrosine phosphorylation or intracellular calcium mobilization. Intravital imaging confirmed that Pxn-KD enhanced thrombus formation in vivo.

Conclusions

Our findings suggest that paxillin negatively regulates several common platelet signaling pathways, resulting in the activation of integrin αIIbβ3 and release reactions.

【 授权许可】

   
2014 Sakata et al.; licensee BioMed Central Ltd.

【 图 表 】

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