Our lab is focused on the question of how cells dynamically assemble and reorganize their actin cytoskeletons to govern cell shape, cell movement, and cell division. Every cell type has a unique architecture tailored to its physiological functions, which is defined in large part by its cytoskeleton. The cytoskeleton is a vast system of interconnected polymeric tubes and fibers that creates a dynamic scaffold used to produce polarity and compartmentalization, and to generate force. The primary aim of our research is to understand how cells bring about rapid and precise rearrangements of their actin polymer networks, transforming cell shape and function.
Actin filament networks are complex, self-assembling biological machines built from hundreds of distinct components and moving parts. We have been dissecting the inner workings of these force-producing machines, analyzing the cellular functions and biochemical mechanisms of actin regulatory proteins in order to understand how this machinery collectively orchestrates the assembly, reorganization, and disassembly of entire actin networks. Our goal is to obtain a highly mechanistic and quantitative view of these events.
We use two different in vivo systems: (a) the budding yeast S. cerevisiae, which offers advanced genetic analyses; and (b) mammalian fibroblasts and primary cardiomyocytes, which offer superior cytology and enable us to study actin regulation underlying cell motility and muscle contraction. Two fundamental questions are being addressed in the lab:
- How is the rapid assembly and disassembly of actin networks governed? To answer this question, we are studying the roles of crucial actin regulatory proteins that alter polymer dynamics, e.g. formins, Arp2/3 complex, and ADF/cofilin (figure 1). We have also identified novel binding partners of these regulators that have surprising new activities. This work includes the characterization of: (a) yeast and mammalian formins, (b) formin-binding proteins (e.g. APC, Bud6, Bud14 and Smy1), (c) WASp-Arp2/3 complex binding partners (e.g. Abp1, Syp1, coronin, and GMF), and (d) the actin disassembly and turnover machinery (e.g. Aip1, coronin, twinfilin, and Srv2/CAP).
- How is the regulation of actin dynamics coordinated with regulation of other cytoskeletal polymer systems (microtubules, septins, and intermediate filaments)? Our recent work in this area addresses functional cross-talk between the actin and microtubule cytoskeletons regulated by a triad of mammalian proteins that physically associate: (a) the tumor suppressor protein Adenomatous polyposis coli (APC), (b) the formin Dia1, and (c) the microtubule end-binding protein EB
To answer the questions above, we are taking a multidisciplinary approach combining genetics, biochemistry, structural biology, and live cell imaging. In vitro analyses include quantitative fluorescence-based kinetic assays, time lapse TIRF microscopy on individual actin filaments, single molecule analysis on actin regulatory proteins, and reconstituted actin-based bead motility assays in cell extracts and purified systems. In vivo analyses include forward and reverse genetic screens, RNAi silencing, live-cell imaging to track cytoskeletal regulatory protein dynamics and polymer dynamics, and electron microscopy (figure 2).
Recent Publications (2008-present)
Chesarone-Cataldo, M., C. Guérin, J.H. Yu, R. Wedlich-Soldner, L. Blanchoin, and B.L. Goode (2011). The myosin-passenger protein Smy1 controls actin cable structure and dynamics by acting as a formin damper. Developmental Cell (in press).
Breitsprecher, D., S.A. Koestler, I. Chizhov, B.L. Goode, K. Rottner, and J. Faix (2011). Cofilin cooperates with fascin to disassemble filopodial actin filaments. J. Cell Sci. (in press).
Gould, C.J., S. Maiti, A. Michelot, B. Graziano, L. Blanchoin, and B.L. Goode (2011). The formin DAD domain plays dual roles in autoinhibition and actin nucleation. Curr. Biol. 21:384-90. [abstract]
Tu, D., Y. Li, H,K. Song, A.V. Toms, C.J. Gould, S.B. Ficarro, J.A. Marto, B.L. Goode and M.J. Eck (2011). Crystal structure of a coiled-coil domain from human ROCK. PLOS One 6(3):e18080.
Huang, W., S. Ghisletti, K. Saijo, M. Gandhi, M. Aouadi, G.J. Tesz, D.X. Zhang, J. Yao, M.P. Czech, B.L. Goode, M.G. Rosenfeld, and C.K. Glass (2011). Coronin 2A mediates actin-dependent derepression of inflammatory response genes. Nature 470:414-8. [abstract]
Gandhi, M., M. Jangi, and B.L. Goode (2010). Identification of conserved surfaces of coronin required for actin binding and in vivo functions. J. Biol. Chem. 285:34899-908.
Okada, K., F. Bartoloni, A. Deaconescu, J.B. Moseley, Z. Dogic, N. Grigorieff, G.G. Gundersen, and B.L. Goode (2010). Adenomatous polyposis coli protein nucleates actin assembly and synergizes with the formin mDia1. J. Cell Biol. 189(7):1087-96. [abstract]
Gandhi, M., B. Smith, M. Bovellan, V. Paavilainen, K. Daugherty-Clarke, J. Gelles, P. Lappalainen, and B.L. Goode (2010). GMF is a cofilin homologue that binds Arp2/3 complex to stimulate filament debranching and inhibit actin nucleation. Curr. Biol. 20:1-7. [abstract]
Balcer, H.I., K. Daugherty-Clarke, and B.L. Goode (2010). Mapping surfaces on the p40/ARPC1 subunit of Arp2/3 complex required for actin nucleation and in vivo function. J. Biol. Chem. 285:8481-91. [abstract]
Chaudhry, F., L. Talarico, K. Little, O. Quintero-Monzon, and B.L. Goode (2010). A central role for the WH2 domain of Srv2/CAP in recharging actin monomers to drive actin turnover in vitro and in vivo. Cytoskel. 67:120-33. [abstract]
Chesarone, M., DuPage, A.G., and B.L. Goode (2009). Unleashing formins to remodel the actin and microtubule cytoskeletons. Nat. Rev. Mol. Cell Biol. 11:62-74. [abstract]
Boettner, D., J.L. D’Agostino, T. Torres, K. Daugherty-Clarke, A. Uyger, A. Reider, B. Wendland, S. Lemmon, and B.L. Goode (2009). The F-BAR domain protein Syp1 negatively regulates WASp-Arp2/3 complex activity during endocytic patch formation. Curr. Biol. 19:1979-87. [abstract]
Gandhi, M., V. Achard, L. Blanchoin, and B.L. Goode (2009). Coronin switches roles in actin disassembly depending on the nucleotide state of actin. Mol. Cell. 34:364-374.[abstract]
Quintero-monzon, O., E.M. Jonasson, E. Bertling, L. Talarico, F. Chaudhry, M. Sihvo, P. Lappalainen, and B.L. Goode (2009). Dissection of the 600 kDa Srv2/CAP complex: roles for oligomerization and binding to cofilin-actin complexes in driving actin turnover. J. Biol. Chem. 284:10923-10934. [abstract]
Chesarone, M., C.J. Gould, J.B. Moseley, and B.L. Goode (2009). Displacement of formins from growing barbed ends by Bud14 is critical for proper actin network architecture and function. Dev. Cell 16:292-302. [abstract]
Chesarone, M., and B.L. Goode (2009). Actin nucleation and elongation factors: mechanisms and interplay. Curr. Opin. Cell Biol. 21:28-37. [abstract]
Stroupe, M.E., C. Xu, B.L. Goode, and N. Grigorieff (2009). Actin filament labels for localizing protein components in large complexes viewed by electron microscopy. RNA 15:244-248. [abstract]
Daugherty-Clarke, K., and B.L. Goode (2008). WASp identity theft by a bacterial effector. Dev. Cell 15:333-334. [abstract]
Bartoloni, F., J.B. Moseley, J. Schmoranzer, L. Cassimeris, B.L. Goode, and G. Gundersen (2008). The formin mDia2 stabilizes microtubules independently of its actin nucleating activity. J. Cell Biol. 181:523-536. [full text in PubMed Central] [abstract]
Daugherty, K., and B.L. Goode (2008). Identification of surfaces on the p35/ARPC2 subunit of Arp2/3 complex required for cell growth, actin nucleation, and endocytosis. J. Biol. Chem 283:16950-16959. [abstract]
Yonetani, A., R.J. Lustig, J.B. Moseley, T. Takeda, B.L. Goode, and F. Chang (2008). Regulation and targeting of the fission yeast formin Cdc12p in cytokinesis. Mol. Biol. Cell. 19:2208-2219. [full text in PubMed Central] [abstract]
Gandhi, M., and B.L. Goode (2008). Coronin: the double-edged sword of actin dynamics. In “The Coronin family of actin binding proteins,” Editor: C. Clemens. Landes Bioscience. [abstract]
View Complete Publication List on PubMed: Bruce Goode
Last review: August 9, 2011