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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM066311-10
Application #
8464143
Study Section
Special Emphasis Panel (ZRG1-CB-D)
Project Start
Project End
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
10
Fiscal Year
2013
Total Cost
$272,704
Indirect Cost
$2,482
Name
Yale University
Department
Type
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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Page, Christopher; Hanein, Dorit; Volkmann, Niels (2015) Accurate membrane tracing in three-dimensional reconstructions from electron cryotomography data. Ultramicroscopy 155:20-6
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
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
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
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
Yi, Kexi; Rubinstein, Boris; Li, Rong (2013) Symmetry breaking and polarity establishment during mouse oocyte maturation. Philos Trans R Soc Lond B Biol Sci 368:20130002
Pollard, Thomas D (2013) No question about exciting questions in cell biology. PLoS Biol 11:e1001734

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