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.
|Anderson, Karen L; Page, Christopher; Swift, Mark F et al. (2017) Nano-scale actin-network characterization of fibroblast cells lacking functional Arp2/3 complex. J Struct Biol 197:312-321|
|Wang, Pei-Shan; Chou, Fu-Sheng; Ramachandran, Sreekumar et al. (2016) Crucial roles of the Arp2/3 complex during mammalian corticogenesis. Development 143:2741-52|
|Pollard, Thomas D (2016) Actin and Actin-Binding Proteins. Cold Spring Harb Perspect Biol 8:|
|Page, Christopher; Hanein, Dorit; Volkmann, Niels (2015) Accurate membrane tracing in three-dimensional reconstructions from electron cryotomography data. Ultramicroscopy 155:20-26|
|Jurgenson, Christopher T; Pollard, Thomas D (2015) Crystals of the Arp2/3 complex in two new space groups with structural information about actin-related protein 2 and potential WASP binding sites. Acta Crystallogr F Struct Biol Commun 71:1161-8|
|Li, Yongchao; Wang, Pei-Shan; Lucas, George et al. (2015) ARP2/3 complex is required for directional migration of neural stem cell-derived oligodendrocyte precursors in electric fields. Stem Cell Res Ther 6:41|
|Tee, Yee Han; Shemesh, Tom; Thiagarajan, Visalatchi et al. (2015) Cellular chirality arising from the self-organization of the actin cytoskeleton. Nat Cell Biol 17:445-57|
|Suraneni, Praveen; Fogelson, Ben; Rubinstein, Boris et al. (2015) A mechanism of leading-edge protrusion in the absence of Arp2/3 complex. Mol Biol Cell 26:901-12|
|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|
|Volkmann, Niels (2014) The joys and perils of flexible fitting. Adv Exp Med Biol 805:137-55|
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