Other
11 Authors
- Chen X,
- White GC 2nd,
- Ma YQ,
- Bialkowska K,
- Pluskota E,
- Plow EF,
- Gao J,
- Liu J,
- Zhi H,
- Byzova TV,
- Xu Z
| First Author | Xu Z | Year | 2014 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 34 |
| Issue | 9 | Pages | 1961-7 |
| PubMed ID | 24969775 | Mgi Jnum | J:227094 |
| Mgi Id | MGI:5699662 | Doi | 10.1161/ATVBAHA.114.303851 |
| Citation | Xu Z, et al. (2014) Direct interaction of kindlin-3 with integrin alphaIIbbeta3 in platelets is required for supporting arterial thrombosis in mice. Arterioscler Thromb Vasc Biol 34(9):1961-7 |
| abstractText | OBJECTIVE: Kindlin-3 is a critical supporter of integrin function in platelets. Lack of expression of kindlin-3 protein in patients impairs integrin alphaIIbbeta3-mediated platelet aggregation. Although kindlin-3 has been categorized as an integrin-binding partner, the functional significance of the direct interaction of kindlin-3 with integrin alphaIIbbeta3 in platelets has not been established. Here, we evaluated the significance of the binding of kindlin-3 to integrin alphaIIbbeta3 in platelets in supporting integrin alphaIIbbeta3-mediated platelet functions. APPROACH AND RESULTS: We generated a strain of kindlin-3 knockin (K3KI) mice that express a kindlin-3 mutant that carries an integrin-interaction defective substitution. K3KI mice could survive normally and express integrin alphaIIbbeta3 on platelets similar to their wild-type counterparts. Functional analysis revealed that K3KI mice exhibited defective platelet function, including impaired integrin alphaIIbbeta3 activation, suppressed platelet spreading and platelet aggregation, prolonged tail bleeding time, and absence of platelet-mediated clot retraction. In addition, whole blood drawn from K3KI mice showed resistance to in vitro thrombus formation and, as a consequence, K3KI mice were protected from in vivo arterial thrombosis. CONCLUSIONS: These observations demonstrate that the direct binding of kindlin-3 to integrin alphaIIbbeta3 is involved in supporting integrin alphaIIbbeta3 activation and integrin alphaIIbbeta3-dependent responses of platelets and consequently contributes significantly to arterial thrombus formation. |
