Characterization of two classes of small molecule inhibitors of Arp2/3 complex

B. J. Nolen, N. Tomasevic, A. Russell, D. W. Pierce, Z. Jia, C. D. McCormick, J. Hartman, R. Sakowicz and T. D. Pollard ()
Additional contact information
B. J. Nolen: Department of Molecular Cellular and Developmental Biology,
N. Tomasevic: Cytokinetics, Inc., South San Francisco, California 94080, USA
A. Russell: Cytokinetics, Inc., South San Francisco, California 94080, USA
D. W. Pierce: Cytokinetics, Inc., South San Francisco, California 94080, USA
Z. Jia: Cytokinetics, Inc., South San Francisco, California 94080, USA
C. D. McCormick: Yale University, New Haven, Connecticut 06520, USA
J. Hartman: Cytokinetics, Inc., South San Francisco, California 94080, USA
R. Sakowicz: Cytokinetics, Inc., South San Francisco, California 94080, USA
T. D. Pollard: Department of Molecular Cellular and Developmental Biology,

Nature, 2009, vol. 460, issue 7258, 1031-1034

Abstract: New Arp2/3 complex inhibitors The actin cytoskeleton is dynamic and plays a critical role in several cell biological processes such as cell adhesion, migration and endocytosis. In addition, several pathogens exploit this system to invade and survive within host cells. The Arp2/3 complex nucleates actin filaments and has a unique property to form branched actin networks. In this study, Nolen et al. describe the generation of two types of small molecules that bind to different sites on the Arp2/3 complex and inhibit its actin nucleating activity in vitro and in vivo. These inhibitors provide a powerful approach to study Arp2/3 complex-mediated actin reorganization events in living cells.

Date: 2009
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DOI: 10.1038/nature08231

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