The long-term goals of the Program Project include the development of a detailed mechanistic model for actin filament branching mediated by the Arp2/3 complex and to characterize the role of the Arp2/3 complex in directed cell motility. Here, we aim at further characterizing the structures of key intermediates and their interactions along the activation pathway of the Arp2/3 complex (Aim 1).
For Aim 2, we will generate high resolution, three-dimensional (3D) structures of actin networks mediated by the complex in its cellular environment. This should allow us to determine how structural details of the Arp2/3-mediated actin networks are being modified by changes in cellular dynamics. We will apply high-resolution electron cryo-microscopy (cryo-EM), electron cryotomography and image analysis to achieve these aims.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Program Projects (P01)
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Special Emphasis Panel (ZRG1-CB-D)
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Yale University
New Haven
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Volkmann, Niels (2014) The joys and perils of flexible fitting. Adv Exp Med Biol 805:137-55
Volkmann, Niels; Page, Christopher; Li, Rong et al. (2014) Three-dimensional reconstructions of actin filaments capped by Arp2/3 complex. Eur J Cell Biol 93:179-83
Xu, Xiao-Ping; Slaughter, Brian D; Volkmann, Niels (2013) Probabilistic determination of probe locations from distance data. J Struct Biol 184:75-82
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Yi, Kexi; Rubinstein, Boris; Unruh, Jay R et al. (2013) Sequential actin-based pushing forces drive meiosis I chromosome migration and symmetry breaking in oocytes. J Cell Biol 200:567-76
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Suraneni, Praveen; Rubinstein, Boris; Unruh, Jay R et al. (2012) The Arp2/3 complex is required for lamellipodia extension and directional fibroblast cell migration. J Cell Biol 197:239-51

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