Our long range goal is to understand the molecular mechanisms controlling the assembly and disassembly of actin filaments during cellular locomotion. We will reach beyond simply defining the inventory of molecules that control the actin cytoskeleton to understand mechanisms in terms of the rates of specific reactions. We will use a combination of biochemical, genetic and cellular experiments to test how cells maintain a pool of cytoplasmic actin subunits, initiate new actin filaments and disassemble aged actin filaments. We will focus on Arp2/3 complex (a key initiator of new barbed ends) and WASp/Scar proteins (activators of Arp2/3 complex), and continue work on capping protein (the terminator of assembly), ADF/cofilins (key components of the disassembly mechanism) and profilin (the nucleotide exchange factor for actin), since they are all important components of the system. Genetic studies have established that these proteins are essential for life and mutations in WASp cause a human disease. The challenges are to establish a mechanism that accounts quantitatively for actin filament dynamics in vivo and to identify the molecular connections between external stimuli for movement and the dynamics of the actin cytoskeleton. Detailed analysis of reaction mechanisms and atomic structures will make possible decisive tests for physiological functions. We are confident that general principles about molecular mechanisms in the actin cytoskeleton will emerge from this work.
| Espinoza-Sanchez, Sofia; Metskas, Lauren Ann; Chou, Steven Z et al. (2018) Conformational changes in Arp2/3 complex induced by ATP, WASp-VCA, and actin filaments. Proc Natl Acad Sci U S A 115:E8642-E8651 |
| Arasada, Rajesh; Sayyad, Wasim A; Berro, Julien et al. (2018) High-speed superresolution imaging of the proteins in fission yeast clathrin-mediated endocytic actin patches. Mol Biol Cell 29:295-303 |
| Aydin, Fikret; Courtemanche, Naomi; Pollard, Thomas D et al. (2018) Gating mechanisms during actin filament elongation by formins. Elife 7: |
| Friend, Janice E; Sayyad, Wasim A; Arasada, Rajesh et al. (2018) Fission yeast Myo2: Molecular organization and diffusion in the cytoplasm. Cytoskeleton (Hoboken) 75:164-173 |
| Fujiwara, Ikuko; Zweifel, Mark E; Courtemanche, Naomi et al. (2018) Latrunculin A Accelerates Actin Filament Depolymerization in Addition to Sequestering Actin Monomers. Curr Biol 28:3183-3192.e2 |
| Akamatsu, Matthew; Lin, Yu; Bewersdorf, Joerg et al. (2017) Analysis of interphase node proteins in fission yeast by quantitative and superresolution fluorescence microscopy. Mol Biol Cell 28:3203-3214 |
| Pollard, Thomas D (2017) Nine unanswered questions about cytokinesis. J Cell Biol 216:3007-3016 |
| Pollard, Thomas D (2017) What We Know and Do Not Know About Actin. Handb Exp Pharmacol 235:331-347 |
| Courtemanche, Naomi; Pollard, Thomas D; Chen, Qian (2016) Avoiding artefacts when counting polymerized actin in live cells with LifeAct fused to fluorescent proteins. Nat Cell Biol 18:676-83 |
| Pollard, Thomas D (2016) Actin and Actin-Binding Proteins. Cold Spring Harb Perspect Biol 8: |
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