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David R. Kovar

Professor
drkovar@uchicago.edu
Research Summary
Cells simultaneously assemble and maintain different actin cytoskeleton networks of distinct organizations and dynamics for fundamental processes such as polarization, endocytosis, motility and division. How does a shared pool of actin monomer building blocks self-organize into distinct actin filament networks of specific densities, sizes and function within a common cellular cytoplasm? Our research group is investigating the molecular mechanisms that govern how diverse actin cytoskeleton networks self-organize through (1) competition for a limited supply of actin monomers, (2) network-specific sorting of actin binding proteins, and (3) the effects of different combinations of actin binding proteins on actin filament network organization, dynamics and function. We take advantage of complementary experiments in live cells and with purified components. These interdisciplinary techniques include genetics, time-lapse fluorescence microscopy of cells, biochemistry, biophysics, in vitro reconstitution and multi-color single molecule TIRF microscopy imaging.
Keywords
Cytoskeleton, Cell Division, Cell Polarity, TIRF Microscopy, Single Molecule Imaging, Self-organization
Education
  • Ohio Wesleyan University, Delaware, OH, BA Botany and Microbiology 05/1995
  • Purdue University, West Lafayette, IN, PhD Biological Sciences 05/2001
  • Yale University, New Haven, CT, Postdoctoral Fellow Biochemistry and Biophysics 10/2005
Biosciences Graduate Program Association
Awards & Honors
  • 2011 - BSD Distinguished Educator and Mentor Award University of Chicago
Publications

  1. Acetylation of fission yeast tropomyosin does not promote differential association with cognate formins. Cytoskeleton (Hoboken). 2023 03; 80(3-4):77-92. View in: PubMed

  2. Actin assembly requirements of the formin Fus1 to build the fusion focus. J Cell Sci. 2022 07 01; 135(13). View in: PubMed

  3. Mechanism of actin filament nucleation. Biophys J. 2021 10 19; 120(20):4399-4417. View in: PubMed

  4. Formin Cdc12's specific actin assembly properties are tailored for cytokinesis in fission yeast. Biophys J. 2021 08 03; 120(15):2984-2997. View in: PubMed

  5. LIM domain proteins in cell mechanobiology. Cytoskeleton (Hoboken). 2021 06; 78(6):303-311. View in: PubMed

  6. Stir it up: The role of actin in mitochondrial mixing during mitosis. Dev Cell. 2021 04 19; 56(8):1080-1082. View in: PubMed

  7. F-Actin Cytoskeleton Network Self-Organization Through Competition and Cooperation. Annu Rev Cell Dev Biol. 2020 10 06; 36:35-60. View in: PubMed

  8. Evolutionarily diverse LIM domain-containing proteins bind stressed actin filaments through a conserved mechanism. Proc Natl Acad Sci U S A. 2020 10 13; 117(41):25532-25542. View in: PubMed

  9. Filament Nucleation Tunes Mechanical Memory in Active Polymer Networks. Adv Funct Mater. 2019 Dec 05; 29(49). View in: PubMed

  10. Pseudomonas aeruginosa exoenzyme Y directly bundles actin filaments. J Biol Chem. 2020 03 13; 295(11):3506-3517. View in: PubMed

  11. Wound Healing Coordinates Actin Architectures to Regulate Mechanical Work. Nat Phys. 2019; 15:696-705. View in: PubMed

  12. Chlamydomonas reinhardtii formin FOR1 and profilin PRF1 are optimized for acute rapid actin filament assembly. Mol Biol Cell. 2019 12 15; 30(26):3123-3135. View in: PubMed

  13. Mechanical and kinetic factors drive sorting of F-actin cross-linkers on bundles. Proc Natl Acad Sci U S A. 2019 08 13; 116(33):16192-16197. View in: PubMed

  14. Cofilin drives rapid turnover and fluidization of entangled F-actin. Proc Natl Acad Sci U S A. 2019 06 25; 116(26):12629-12637. View in: PubMed

  15. Cooperation between tropomyosin and a-actinin inhibits fimbrin association with actin filament networks in fission yeast. Elife. 2019 06 10; 8. View in: PubMed

  16. Feeling the force: formin's role in mechanotransduction. Curr Opin Cell Biol. 2019 02; 56:130-140. View in: PubMed

  17. Ena/VASP processive elongation is modulated by avidity on actin filaments bundled by the filopodia cross-linker fascin. Mol Biol Cell. 2019 03 21; 30(7):851-862. View in: PubMed

  18. Actin Cross-Linking Toxin Is a Universal Inhibitor of Tandem-Organized and Oligomeric G-Actin Binding Proteins. Curr Biol. 2018 05 21; 28(10):1536-1547.e9. View in: PubMed

  19. Partitioning and Enhanced Self-Assembly of Actin in Polypeptide Coacervates. Biophys J. 2018 04 10; 114(7):1636-1645. View in: PubMed

  20. Mechanoregulated inhibition of formin facilitates contractile actomyosin ring assembly. Nat Commun. 2017 09 26; 8(1):703. View in: PubMed

  21. When Is "Enough" Enough? Cell Syst. 2017 05 24; 4(5):480-482. View in: PubMed

  22. The bacterial virulence factors VopL and VopF nucleate actin from the pointed end. J Cell Biol. 2017 05 01; 216(5):1267-1276. View in: PubMed

  23. Competition between Tropomyosin, Fimbrin, and ADF/Cofilin drives their sorting to distinct actin filament networks. Elife. 2017 03 10; 6. View in: PubMed

  24. Fascin- and a-Actinin-Bundled Networks Contain Intrinsic Structural Features that Drive Protein Sorting. Curr Biol. 2016 10 24; 26(20):2697-2706. View in: PubMed

  25. Internetwork competition for monomers governs actin cytoskeleton organization. Nat Rev Mol Cell Biol. 2016 12; 17(12):799-810. View in: PubMed

  26. The F-actin bundler a-actinin Ain1 is tailored for ring assembly and constriction during cytokinesis in fission yeast. Mol Biol Cell. 2016 06 01; 27(11):1821-33. View in: PubMed

  27. In Vitro Biochemical Characterization of Cytokinesis Actin-Binding Proteins. Methods Mol Biol. 2016; 1369:151-79. View in: PubMed

  28. ACTIN-DIRECTED TOXIN. ACD toxin-produced actin oligomers poison formin-controlled actin polymerization. Science. 2015 Jul 31; 349(6247):535-9. View in: PubMed

  29. Actin age orchestrates myosin-5 and myosin-6 run lengths. Curr Biol. 2015 Aug 03; 25(15):2057-62. View in: PubMed

  30. Plasmodium falciparum coronin organizes arrays of parallel actin filaments potentially guiding directional motility in invasive malaria parasites. Malar J. 2015 Jul 18; 14:280. View in: PubMed

  31. Disassembly activity of actin-depolymerizing factor (ADF) is associated with distinct cellular processes in apicomplexan parasites. Mol Biol Cell. 2015 Sep 01; 26(17):3001-12. View in: PubMed

  32. Cytoskeletal dynamics: a view from the membrane. J Cell Biol. 2015 May 11; 209(3):329-37. View in: PubMed

  33. Profilin regulates F-actin network homeostasis by favoring formin over Arp2/3 complex. Dev Cell. 2015 Jan 12; 32(1):43-53. View in: PubMed

  34. Profilin-1 serves as a gatekeeper for actin assembly by Arp2/3-dependent and -independent pathways. Dev Cell. 2015 Jan 12; 32(1):54-67. View in: PubMed

  35. Fission yeast profilin is tailored to facilitate actin assembly by the cytokinesis formin Cdc12. Mol Biol Cell. 2015 Jan 15; 26(2):283-93. View in: PubMed

  36. High-resolution temporal analysis reveals a functional timeline for the molecular regulation of cytokinesis. Dev Cell. 2014 Jul 28; 30(2):209-23. View in: PubMed

  37. HopW1 from Pseudomonas syringae disrupts the actin cytoskeleton to promote virulence in Arabidopsis. PLoS Pathog. 2014 Jun; 10(6):e1004232. View in: PubMed

  38. Ena/VASP Enabled is a highly processive actin polymerase tailored to self-assemble parallel-bundled F-actin networks with Fascin. Proc Natl Acad Sci U S A. 2014 Mar 18; 111(11):4121-6. View in: PubMed

  39. Enabled negatively regulates diaphanous-driven actin dynamics in vitro and in vivo. Dev Cell. 2014 Feb 24; 28(4):394-408. View in: PubMed

  40. Homeostatic actin cytoskeleton networks are regulated by assembly factor competition for monomers. Curr Biol. 2014 Mar 03; 24(5):579-85. View in: PubMed

  41. A mechanism for actin filament severing by malaria parasite actin depolymerizing factor 1 via a low affinity binding interface. J Biol Chem. 2014 Feb 14; 289(7):4043-54. View in: PubMed

  42. In vitro reconstitution of an mRNA-transport complex reveals mechanisms of assembly and motor activation. J Cell Biol. 2013 Dec 23; 203(6):971-84. View in: PubMed

  43. Formin-based control of the actin cytoskeleton during cytokinesis. Biochem Soc Trans. 2013 Dec; 41(6):1750-4. View in: PubMed

  44. The formins Cdc12 and For3 cooperate during contractile ring assembly in cytokinesis. J Cell Biol. 2013 Oct 14; 203(1):101-14. View in: PubMed

  45. SIN-dependent phosphoinhibition of formin multimerization controls fission yeast cytokinesis. Genes Dev. 2013 Oct 01; 27(19):2164-77. View in: PubMed

  46. Rickettsia Sca2 has evolved formin-like activity through a different molecular mechanism. Proc Natl Acad Sci U S A. 2013 Jul 16; 110(29):E2677-86. View in: PubMed

  47. Actin assembly factors regulate the gelation kinetics and architecture of F-actin networks. Biophys J. 2013 Apr 16; 104(8):1709-19. View in: PubMed

  48. Assembly kinetics determine the architecture of a-actinin crosslinked F-actin networks. Nat Commun. 2012 May 29; 3:861. View in: PubMed

  49. Mechanism of actin filament nucleation by Vibrio?VopL and implications for tandem W domain nucleation. Nat Struct Mol Biol. 2011 Aug 28; 18(9):1060-7. View in: PubMed

  50. The functionally distinct fission yeast formins have specific actin-assembly properties. Mol Biol Cell. 2011 Oct; 22(20):3826-39. View in: PubMed

  51. Actin filament bundling by fimbrin is important for endocytosis, cytokinesis, and polarization in fission yeast. J Biol Chem. 2011 Jul 29; 286(30):26964-77. View in: PubMed

  52. Minimal requirements for actin filament disassembly revealed by structural analysis of malaria parasite actin-depolymerizing factor 1. Proc Natl Acad Sci U S A. 2011 Jun 14; 108(24):9869-74. View in: PubMed

  53. Three's company: the fission yeast actin cytoskeleton. Trends Cell Biol. 2011 Mar; 21(3):177-87. View in: PubMed

  54. Rickettsia Sca2 is a bacterial formin-like mediator of actin-based motility. Nat Cell Biol. 2010 Nov; 12(11):1057-63. View in: PubMed

  55. Fimbrin and tropomyosin competition regulates endocytosis and cytokinesis kinetics in fission yeast. Curr Biol. 2010 Aug 24; 20(16):1415-22. View in: PubMed

  56. Rationally simplified bistramide analog reversibly targets actin polymerization and inhibits cancer progression in vitro and in vivo. J Am Chem Soc. 2010 Jun 02; 132(21):7288-90. View in: PubMed

  57. Identification and characterization of a small molecule inhibitor of formin-mediated actin assembly. Chem Biol. 2009 Nov 25; 16(11):1158-68. View in: PubMed

  58. Role of tropomyosin in formin-mediated contractile ring assembly in fission yeast. Mol Biol Cell. 2009 Apr; 20(8):2160-73. View in: PubMed

  59. Incompatibility with formin Cdc12p prevents human profilin from substituting for fission yeast profilin: insights from crystal structures of fission yeast profilin. J Biol Chem. 2009 Jan 23; 284(4):2088-97. View in: PubMed

  60. Formin differentially utilizes profilin isoforms to rapidly assemble actin filaments. J Biol Chem. 2009 Jan 02; 284(1):673-684. View in: PubMed

  61. The cytokinesis formins from the nematode worm and fission yeast differentially mediate actin filament assembly. J Biol Chem. 2008 Aug 29; 283(35):23872-83. View in: PubMed

  62. Intracellular motility: myosin and tropomyosin in actin cable flow. Curr Biol. 2007 Apr 03; 17(7):R244-7. View in: PubMed

  63. Attachment conditions control actin filament buckling and the production of forces. Biophys J. 2007 Apr 01; 92(7):2546-58. View in: PubMed

  64. Arp2/3 ATP hydrolysis: to branch or to debranch? Nat Cell Biol. 2006 Aug; 8(8):783-5. View in: PubMed

  65. Assembly of the cytokinetic contractile ring from a broad band of nodes in fission yeast. J Cell Biol. 2006 Jul 31; 174(3):391-402. View in: PubMed

  66. Cell polarity: formin on the move. Curr Biol. 2006 Jul 25; 16(14):R535-8. View in: PubMed

  67. Twinfilin is an actin-filament-severing protein and promotes rapid turnover of actin structures in vivo. J Cell Sci. 2006 Apr 15; 119(Pt 8):1547-57. View in: PubMed

  68. Model of formin-associated actin filament elongation. Mol Cell. 2006 Feb 17; 21(4):455-66. View in: PubMed

  69. Control of the assembly of ATP- and ADP-actin by formins and profilin. Cell. 2006 Jan 27; 124(2):423-35. View in: PubMed

  70. Molecular details of formin-mediated actin assembly. Curr Opin Cell Biol. 2006 Feb; 18(1):11-7. View in: PubMed

  71. Profilin-mediated competition between capping protein and formin Cdc12p during cytokinesis in fission yeast. Mol Biol Cell. 2005 May; 16(5):2313-24. View in: PubMed

  72. Progressing actin: Formin as a processive elongation machine. Nat Cell Biol. 2004 Dec; 6(12):1158-9. View in: PubMed

  73. A plant-specific kinesin binds to actin microfilaments and interacts with cortical microtubules in cotton fibers. Plant Physiol. 2004 Dec; 136(4):3945-55. View in: PubMed

  74. Insertional assembly of actin filament barbed ends in association with formins produces piconewton forces. Proc Natl Acad Sci U S A. 2004 Oct 12; 101(41):14725-30. View in: PubMed

  75. Structure of the actin crosslinking core of fimbrin. Structure. 2004 Jun; 12(6):999-1013. View in: PubMed

  76. Spatial and temporal pathway for assembly and constriction of the contractile ring in fission yeast cytokinesis. Dev Cell. 2003 Nov; 5(5):723-34. View in: PubMed

  77. Arabidopsis capping protein (AtCP) is a heterodimer that regulates assembly at the barbed ends of actin filaments. J Biol Chem. 2003 Nov 07; 278(45):44832-42. View in: PubMed

  78. The fission yeast cytokinesis formin Cdc12p is a barbed end actin filament capping protein gated by profilin. J Cell Biol. 2003 Jun 09; 161(5):875-87. View in: PubMed

  79. Signal-mediated depolymerization of actin in pollen during the self-incompatibility response. Plant Cell. 2002 Oct; 14(10):2613-26. View in: PubMed

  80. Chlamydomonas reinhardtii produces a profilin with unusual biochemical properties. J Cell Sci. 2001 Dec; 114(Pt 23):4293-305. View in: PubMed

  81. Actin and actin-binding proteins in higher plants. Protoplasma. 2001; 215(1-4):89-104. View in: PubMed

  82. Fluorescently-labeled fimbrin decorates a dynamic actin filament network in live plant cells. Planta. 2001 Jul; 213(3):390-5. View in: PubMed

  83. The characterization of ligand-specific maize (Zea mays) profilin mutants. Biochem J. 2001 Aug 15; 358(Pt 1):49-57. View in: PubMed

  84. AtFim1 is an actin filament crosslinking protein from Arabidopsis thaliana. Plant J. 2000 Dec; 24(5):625-36. View in: PubMed

  85. Technical advance: identification of plant actin-binding proteins by F-actin affinity chromatography. Plant J. 2000 Oct; 24(1):127-37. View in: PubMed

  86. Characterization of Ricinus communis phloem profilin, RcPRO1. Plant Mol Biol. 2000 Mar; 42(5):719-30. View in: PubMed

  87. Maize profilin isoforms are functionally distinct. Plant Cell. 2000 Apr; 12(4):583-98. View in: PubMed

  88. Latrunculin B has different effects on pollen germination and tube growth. Plant Cell. 1999 Dec; 11(12):2349-63. View in: PubMed

  89. Pollen profilin function depends on interaction with proline-rich motifs. Plant Cell. 1998 Jun; 10(6):981-93. View in: PubMed
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