title: Paxillin is an intrinsic negative regulator of platelet activation in mice.
abstract: 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.
  
  
  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.
authors.forename: Asuka
authors.initials: A
authors.lastname: Sakata
authors.affiliation: 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. tohmori@jichi.ac.jp.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Ohmori
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nishimura
authors.forename: Hidenori
authors.initials: H
authors.lastname: Suzuki
authors.forename: Seiji
authors.initials: S
authors.lastname: Madoiwa
authors.forename: Jun
authors.initials: J
authors.lastname: Mimuro
authors.forename: Kazuomi
authors.initials: K
authors.lastname: Kario
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sakata