Our lab is captivated by the question of how cells control the rapid assembly and turnover of actin polymer networks 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 produce forces that underlie cell morphogenesis, cell movement, and cell division. The major goal of our research is to understand how cells bring about precise rearrangements of their actin polymer networks, transforming cell shape and function. With hundreds of distinct components and interacting moving parts, actin arrays can be considered self-assembling, work-producing biological machines. Cells deploy a battery of proteins with different, specialized effects to remodel their actin cytoskeletons in response to signals. The goal of our lab is to gain a highly mechanistic and quantitative view of these events.

We are focused on two fundamental questions. (1) How is the rapid assembly and disassembly of the actin cytoskeleton governed to produce mechanical forces driving cell motility, endocytosis, polarized growth,
and cell division? More specifically, we are defining the in vivo functions and biochemical mechanisms of key, conserved actin-associated proteins (e.g. formins, Arp2/3 complex, cofilin) that bring about dynamic rearrangements in actin networks (figure 1). Our work has defined novel binding partners for many of these players, and revealed surprising new activities at work. This has included the activities of yeast and mammalian formins, a number of formin-binding proteins (e.g. Bud6 and Bud14), Arp2/3 complex-interacting factors (e.g. WASp, Abp1 and coronin), and the actin turnover machinery (e.g. Aip1, twinfilin, and Srv2/CAP). (2) How do other cytoskeletal systems found in eukaryotic cells (microtubules, septins, and intermediate filaments) cooperate with actin polymers to regulate these cellular processes?

To answer these questions, our lab takes a multidisciplinary approach combining genetics, biochemistry, structural biology, and live cell imaging. In vitro analyses include quantitative kinetic assays, time lapse TIRF microscopy imaging of individual actin filaments, and assays in cell extracts. In vivo analyses are performed in two complementary systems, budding yeast (S. cerevisiae), which provide advanced genetic
tractability, and mammalian cells, which offer superior cytology. Most of our published work has used yeast, but over recent years our projects have branched into mammalian cells (muscle and neurons). We are using multi-wavelength live-cell imaging to track the dynamics of actin regulatory proteins in vivo (figure 2), in parallel with single molecule TIRF microscopy to study protein interactions and dynamics in vitro.

Selected Publications

Coronin switches roles in actin disassembly depending on the nucleotide state of actin. Gandhi M, Achard V, Blanchoin L, Goode BL. Mol Cell. 2009 May 15;34(3):364-74.

Reconstitution and dissection of the 600-kDa Srv2/CAP complex: roles for oligomerization and cofilin-actin binding in driving actin turnover. Quintero-Monzon O, Jonasson EM, Bertling E, Talarico L, Chaudhry F, Sihvo M, Lappalainen P, Goode BL. J Biol Chem. 2009 Apr 17;284(16):10923-34.

Chesarone M, Gould CJ, Moseley JB, Goode BL. Displacement of formins from growing barbed ends by bud14 is critical for actin cable architecture and function. Dev Cell. 2009 Feb;16(2):292-302. [abstract]

Chesarone MA, Goode BL. Actin nucleation and elongation factors: mechanisms and interplay. Curr Opin Cell Biol. 2009.2009 Feb;21(1):28-37. [abstract]

Stroupe ME, Xu C, Goode BL, Grigorieff N. Actin filament labels for localizing protein components in large complexes viewed by electron microscopy. RNA. 2009 Feb;15(2):244-8. [abstract]

Yonetani A, Lustig RJ, Moseley JB, Takeda T, Goode BL, Chang F. Regulation and targeting of the fission yeast formin cdc12p in cytokinesis. Mol Biol Cell. 2008 May;19(5):2208-19. [full text in PubMed Central] [abstract]

Gandhi M, Goode BL. Coronin: the double-edged sword of actin dynamics. Subcell Biochem. 2008;48:72-87. Subcell Biochem. 2008;48:72-87. [abstract]

Daugherty-Clarke K, Goode BL. WASp identity theft by a bacterial effector. Dev Cell. 2008;15(3):333-4. [abstract]

Daugherty KM, Goode BL. Functional surfaces on the p35/ARPC2 subunit of Arp2/3 complex required for cell growth, actin nucleation, and endocytosis. J Biol Chem. 2008;283(24):16950-9. [abstract]

Bartolini F, Moseley JB, Schmoranzer J, Cassimeris L, Goode BL, Gundersen GG. The formin mDia2 stabilizes microtubules independently of its actin nucleation activity. J Cell Biol. 2008;181(3):523-36. [full text in PubMed Central] [abstract]

Sokolova O, Maiti S, Grigorieff N, Lappalainen P, Goode BL. Conformational changes in actin-binding proteins, revealed by single particle electron microscopy. Febs Journal. 2007;274:107.

Moseley JB, Bartolini F, Okada K, Wen Y, Gundersen GG, Goode BL. Regulated binding of adenomatous polyposis coli protein to actin. J Biol Chem. 2007;282(17):12661-8. [abstract]

Lu J, Meng W, Poy F, Maiti S, Goode BL, Eck MJ. Structure of the FH2 domain of Daam1: implications for formin regulation of actin assembly. J Mol Biol. 2007;369(5):1258-69. [full text in PubMed Central] [abstract]

Goode BL, Eck MJ. Mechanism and Function of Formins in Control of Actin Assembly. Annu Rev Biochem. 2007;76:593-627.[abstract]

Bertling E, Quintero-Monzon O, Mattila PK, Goode BL, Lappalainen P. Mechanism and biological role of profilin-Srv2/CAP interaction. J Cell Sci. 2007;120(Pt 7):1225-34. [abstract]

Okada K, Ravi H, Smith EM, Goode BL. Aip1 and Cofilin Promote Rapid Turnover of Yeast Actin Patches and Cables: A Coordinated Mechanism for Severing and Capping Filaments. Mol Biol Cell. 2006 Jul;17(7):2855-68. [abstract]

Moseley JB, Okada K, Balcer HI, Kovar DR, Pollard TD, Goode BL. Twinfilin is an actin-filament-severing protein and promotes rapid turnover of actin structures in vivo. J Cell Sci. 2006;119(Pt 8):1547-57. [abstract]

Moseley JB, Maiti S, Goode BL. Formin proteins: purification and measurement of effects on actin assembly. Methods Enzymol. 2006;406:215-34. [abstract]

Moseley JB, Goode BL. The yeast actin cytoskeleton: from cellular function to biochemical mechanism. Microbiol Mol Biol Rev. 2006;70(3):605-45. [abstract]

Gandhi M, Goode BL, Chan CS. Four novel suppressors of gic1 gic2 and their roles in cytokinesis and polarized cell growth in S. cerevisiae. Genetics. 2006. [abstract]

Rodal AA, Sokolova O, Robins DB, Daugherty KM, Hippenmeyer S, Riezman H, et al. Conformational changes in the Arp2/3 complex leading to actin nucleation. Nat Struct Mol Biol. 2005;12(1):26-31. [abstract]

Rodal AA, Kozubowski L, Goode BL, Drubin DG, Hartwig JH. Actin and septin ultrastructures at the budding yeast cell cortex. Mol Biol Cell. 2005;16(1):372-84. [abstract]

Quintero-Monzon O, Rodal AA, Strokopytov B, Almo SC, Goode BL. Structural and Functional Dissection of the Abp1 ADFH Actin-binding Domain Reveals Versatile In Vivo Adapter Functions. Mol Biol Cell. 2005;16(7):3128-39. [abstract]

Moseley JB, Goode BL. Differential activities and regulation of Saccharomyces cerevisiae formin proteins Bni1 and Bnr1 by Bud6. J Biol Chem. 2005;280(30):28023-33. [abstract]

D'Agostino JL, Goode BL. Dissection of Arp2/3 Complex Actin Nucleation Mechanism and Distinct Roles for Its Nucleation-Promoting Factors in Saccharomyces cerevisiae. Genetics. 2005;171(1):35-47. [abstract]

 

View Complete Publication List on PubMed: Bruce Goode

Last review: July 14, 2009