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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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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Li, Rong; Albertini, David F (2013) The road to maturation: somatic cell interaction and self-organization of the mammalian oocyte. Nat Rev Mol Cell Biol 14:141-52
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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
Volkmann, Niels (2012) Putting structure into context: fitting of atomic models into electron microscopic and electron tomographic reconstructions. Curr Opin Cell Biol 24:141-7
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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