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Blood, 15 April 2005, Vol. 105, No. 8, pp. 3141-3148.
Prepublished online as a Blood First Edition Paper on August 3, 2004July 27, 2004; DOI 10.1182/blood-2003-04-1319.
Previous Article | Next Article 
Submitted April 28, 2003
Accepted June 28, 2004
WAVE/Scars in Platelets
Atsushi Oda*, Hiroaki Miki, Ikuo Wada, Hideki Yamaguchi, Daisuke Yamazaki, Suetsugu Shiro, Nakajima Mineba, Nakayama Akira, Katsuya Okawa, Hiroshi Miyazaki, Kazuhiko Matsuno, Hans D Ochs, Laura M Machesky, Hiroyoshi Fujita, and Tadaomi Takenawa
Laboratory of Environmental Biology, Department of Preventive Medicine, Hokkaido University School of Medicine, Sapporo, Hokkaido, Japan
Department of Biochemistry, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan; JST, PRESTO, Japan
Department of Cell Science, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima, Japan
Department of Biochemistry, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan
Horizontal Medical Research Organization, Kyoto University Faculty of Medicine, Kyoto, Japan
Pharmaceutical Division, Pharmaceutical Research Laboratories, Kirin Brewery Co., ltd., Takasaki, Gunma, Japan
College of Medical Technology and School of Medicine, Hokkaido University, Sapporo, Japan
Division of Immunology, Infectious Diseases and Rheumatology, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA
School of Biosciences, Div. of Mol. Cell Biol., University of Birmingham, Birmingham, United Kingdom
* Corresponding author; email: aoda{at}med.hokudai.ac.jp.
Using specific antibodies against isoforms of WAVE (WASP family Verprolin-homologous protein, also called Scar), we demonstrated that human platelets express all three isoforms. Using an in vitro pull-down technique, the src homology 3 (SH3) domain of IRS-p53 precipitated WAVE2 from platelet lysates more efficiently than Profilin I did. The opposite was true for WAVE1, and neither precipitated WAVE3, suggesting that WAVE isoforms have different affinities to these ligands, while the SH3 domain of abl binds to all three isoforms. The three WAVE isoforms were distributed in the actin-rich Triton X-100 insoluble pellets following platelet aggregation induced by thrombin-receptor activating peptide. We also found that all three WAVE isoforms are substrates for calpain in vivo and in vitro. Although portions of these three isoforms were commonly distributed in the actin and Arp2/3-rich edge of the lamellipodia in spreading platelets, only WAVE2 remained in the cell fringe following detergent extraction/fixation of the cells. Finally, by mass spectrometry, we found that the proteins, which reportedly interact with WAVE/Scars, are present in platelets. These data suggest that the three WAVE isoforms exhibit common and distinct features, and may potentially be involved in the regulation of actin cytoskeleton in platelets

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