This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture in Japan, Yamanouchi Foundation for Research and Metabolic Disorders (Tsukuba, Japan), and Mitsubishi Pharma Research Foundation (Osaka, Japan).
Expression and subcellular localization of WAVE isoforms in the megakaryocyte/platelet lineage
Article first published online: 6 DEC 2004
Journal of Thrombosis and Haemostasis
Volume 3, Issue 2, pages 361–368, February 2005
How to Cite
KASHIWAGI, H., SHIRAGA, M., KATO, H., HONDA, S., SAKO, M., KURATA, Y., KANAKURA, Y. and TOMIYAMA, Y. (2005), Expression and subcellular localization of WAVE isoforms in the megakaryocyte/platelet lineage. Journal of Thrombosis and Haemostasis, 3: 361–368. doi: 10.1111/j.1538-7836.2004.01082.x
- Issue published online: 6 DEC 2004
- Article first published online: 6 DEC 2004
- Received 24 June 2004, accepted 20 September 2004
Summary. WAVE isoforms, which consist of WAVE-1, WAVE-2 and WAVE-3, are members of the Wiskott–Aldrich syndrome protein (WASP) family. They are implicated in the regulation of actin-cytoskeletal reorganization downsteam of the small GTPase, Rac. Since platelet attachment to extracellular matrices leads to filopodial and lamellipodial extension, we examined the expression and subcellular localization of WAVEs in platelets. Employing primary megakaryocytic cells derived from cord blood as well as megakaryocytic cell lines, we also examined their expression during megakaryocytic differentiation. Immunoblotting and immunohistochemical analysis revealed that platelets expressed WAVE-1 and WAVE-2, whereas WAVE-3 expression was hardly to be detected. WAVE-1 expression was associated with megakaryocytic differentiation, whereas WAVE-2 and WAVE-3 expression was not changed by the differentiation. In adhered platelets both WAVE-1 and WAVE-2 were localized at the edge of the lamellipodia and at the tips of filopodia. In WASP-deficient platelets we found normal lamellipodial formation and localization of WAVE-1 and WAVE-2 at the edges of lamellipodia. Furthermore, we demonstrated that WAVE-1 and WAVE-2 moved from a detergent-soluble cytosolic fraction to insoluble cytoskeleton fraction after platelet aggregation. These results suggest that WAVE-1 and WAVE-2 regulate actin reorganization during platelet spreading and aggregate formation.