Michael A. Glotzer

Research Summary
The Glotzer lab focuses on questions related to cell organization. How do cells coordinate the position of the contractile ring with the position of the spindle? By what mechanisms are cortical domains that mediate cell polarization assembled and maintained? How do cells regulate cortical contractility during developmental morphogenesis? To answer these questions, we use the nematode C. elegans, cultured human cells, budding yeast, and Drosophila as model systems and we combine forward and reverse genetics, biochemistry, and live cell imaging. Through these approaches we have discovered and extensively characterized the centralspindlin complex, a multifunctional protein complex that regulates essentially every step of cytokinesis. We have pioneered the use of optogenetics to dissect spatiotemporally regulated processes. Using these approaches, we have demonstrated that RhoA activation is sufficient to induce cleavage furrows irrespective of the position of the spindle or the stage of the cell cycle. Likewise, we obtained direct evidence that positive feedback is active during yeast cell polarization. By combining optogenetics with "conventional" genetics and live cell imaging we can directly test models for how cells endow well defined cortical regions with distinct properties that are required for complex cellular events, like cell division, cell polarization, and tissue scale morphogenetic events, such as gastrulation.
Keywords
Cytokinesis, Rho GTPases, Cell Polarity, Optogenetics, Centralspindlin
Education
  • European Molecular Biology Labs, Heidelberg, Germany, Postdoc 09/1997
  • University of California, San Francisco, San Francisco, CA, Ph.D Cell Biology 09/1993
  • University of California, Berkeley, Berkeley, CA, A.B. Mathematics 05/1985
Awards & Honors
  • 2003 - EMBO Member
  • 2004 - Keith Porter Fellow Keith Porter Endowment
Publications
  1. Adriaans IE, Basant A, Ponsioen B, Glotzer M, Lens SMA. PLK1 plays dual roles in centralspindlin regulation during cytokinesis. J Cell Biol. 2019 Apr 01; 218(4):1250-1264. View in: PubMed

  2. Basant A, Glotzer M. Spatiotemporal Regulation of RhoA during Cytokinesis. Curr Biol. 2018 05 07; 28(9):R570-R580. View in: PubMed

  3. Basant A, Glotzer M. A GAP that Divides. F1000Res. 2017; 6:1788. View in: PubMed

  4. Witte K, Strickland D, Glotzer M. Cell cycle entry triggers a switch between two modes of Cdc42 activation during yeast polarization. Elife. 2017 07 06; 6. View in: PubMed

  5. Oakes PW, Wagner E, Brand CA, Probst D, Linke M, Schwarz US, Glotzer M, Gardel ML. Optogenetic control of RhoA reveals zyxin-mediated elasticity of stress fibres. Nat Commun. 2017 06 12; 8:15817. View in: PubMed

  6. Glotzer M. Cytokinesis in Metazoa and Fungi. Cold Spring Harb Perspect Biol. 2017 Oct 03; 9(10). View in: PubMed

  7. Afshar K, Werner ME, Tse YC, Glotzer M, Gönczy P. Regulation of cortical contractility and spindle positioning by the protein phosphatase 6 PPH-6 in one-cell stage C. elegans embryos. Development. 2016 07 15; 143(14):2689. View in: PubMed

  8. Wagner E, Glotzer M. Local RhoA activation induces cytokinetic furrows independent of spindle position and cell cycle stage. J Cell Biol. 2016 06 20; 213(6):641-9. View in: PubMed

  9. Zhang D, Glotzer M. Cytokinesis: Placing the Furrow in Context. Curr Biol. 2015 Dec 21; 25(24):R1183-5. View in: PubMed

  10. Spiltoir JI, Strickland D, Glotzer M, Tucker CL. Optical Control of Peroxisomal Trafficking. ACS Synth Biol. 2016 07 15; 5(7):554-60. View in: PubMed

  11. Zhang D, Glotzer M. The RhoGAP activity of CYK-4/MgcRacGAP functions non-canonically by promoting RhoA activation during cytokinesis. Elife. 2015 Aug 07; 4. View in: PubMed

  12. Basant A, Lekomtsev S, Tse YC, Zhang D, Longhini KM, Petronczki M, Glotzer M. Aurora B kinase promotes cytokinesis by inducing centralspindlin oligomers that associate with the plasma membrane. Dev Cell. 2015 Apr 20; 33(2):204-15. View in: PubMed

  13. White EA, Raghuraman H, Perozo E, Glotzer M. Binding of the CYK-4 subunit of the centralspindlin complex induces a large scale conformational change in the kinesin subunit. J Biol Chem. 2013 Jul 05; 288(27):19785-95. View in: PubMed

  14. Glotzer M. Cytokinesis: centralspindlin moonlights as a membrane anchor. Curr Biol. 2013 Feb 18; 23(4):R145-7. View in: PubMed

  15. White EA, Glotzer M. Centralspindlin: at the heart of cytokinesis. Cytoskeleton (Hoboken). 2012 Nov; 69(11):882-92. View in: PubMed

  16. Tse YC, Werner M, Longhini KM, Labbe JC, Goldstein B, Glotzer M. RhoA activation during polarization and cytokinesis of the early Caenorhabditis elegans embryo is differentially dependent on NOP-1 and CYK-4. Mol Biol Cell. 2012 Oct; 23(20):4020-31. View in: PubMed

  17. Strickland D, Lin Y, Wagner E, Hope CM, Zayner J, Antoniou C, Sosnick TR, Weiss EL, Glotzer M. TULIPs: tunable, light-controlled interacting protein tags for cell biology. Nat Methods. 2012 Mar 04; 9(4):379-84. View in: PubMed

  18. Loria A, Longhini KM, Glotzer M. The RhoGAP domain of CYK-4 has an essential role in RhoA activation. Curr Biol. 2012 Feb 07; 22(3):213-9. View in: PubMed

  19. Tse YC, Piekny A, Glotzer M. Anillin promotes astral microtubule-directed cortical myosin polarization. Mol Biol Cell. 2011 Sep; 22(17):3165-75. View in: PubMed

  20. Glotzer M. Cytokinesis: integrating signaling, the cytoskeleton, and membranes to create new daughter cells. Semin Cell Dev Biol. 2010 Dec; 21(9):865. View in: PubMed

  21. Glotzer M. Controlling cytokinesis through promiscuous phosphorylation outside BARs. Mol Cell. 2010 Jul 09; 39(1):3-5. View in: PubMed

  22. Afshar K, Werner ME, Tse YC, Glotzer M, Gönczy P. Regulation of cortical contractility and spindle positioning by the protein phosphatase 6 PPH-6 in one-cell stage C. elegans embryos. Development. 2010 Jan; 137(2):237-47. View in: PubMed

  23. Hutterer A, Glotzer M, Mishima M. Clustering of centralspindlin is essential for its accumulation to the central spindle and the midbody. Curr Biol. 2009 Dec 15; 19(23):2043-9. View in: PubMed

  24. Wolfe BA, Takaki T, Petronczki M, Glotzer M. Polo-like kinase 1 directs assembly of the HsCyk-4 RhoGAP/Ect2 RhoGEF complex to initiate cleavage furrow formation. PLoS Biol. 2009 May 05; 7(5):e1000110. View in: PubMed

  25. Wolfe BA, Glotzer M. Single cells (put a ring on it). Genes Dev. 2009 Apr 15; 23(8):896-901. View in: PubMed

  26. Glotzer M. Cytokinesis: GAP gap. Curr Biol. 2009 Feb 24; 19(4):R162-5. View in: PubMed

  27. Glotzer M. The 3Ms of central spindle assembly: microtubules, motors and MAPs. Nat Rev Mol Cell Biol. 2009 Jan; 10(1):9-20. View in: PubMed

  28. Slatkin DN, Blattmann H, Wagner HP, Glotzer MA, Laissue JA. Prospects for microbeam radiation therapy of brain tumours in children. Dev Med Child Neurol. 2009 Feb; 51(2):163. View in: PubMed

  29. Simon GC, Schonteich E, Wu CC, Piekny A, Ekiert D, Yu X, Gould GW, Glotzer M, Prekeris R. Sequential Cyk-4 binding to ECT2 and FIP3 regulates cleavage furrow ingression and abscission during cytokinesis. EMBO J. 2008 Jul 09; 27(13):1791-803. View in: PubMed

  30. Werner M, Glotzer M. Control of cortical contractility during cytokinesis. Biochem Soc Trans. 2008 Jun; 36(Pt 3):371-7. View in: PubMed

  31. Kieserman EK, Glotzer M, Wallingford JB. Developmental regulation of central spindle assembly and cytokinesis during vertebrate embryogenesis. Curr Biol. 2008 Jan 22; 18(2):116-23. View in: PubMed

  32. Piekny AJ, Glotzer M. Anillin is a scaffold protein that links RhoA, actin, and myosin during cytokinesis. Curr Biol. 2008 Jan 08; 18(1):30-6. View in: PubMed

  33. Pavicic-Kaltenbrunner V, Mishima M, Glotzer M. Cooperative assembly of CYK-4/MgcRacGAP and ZEN-4/MKLP1 to form the centralspindlin complex. Mol Biol Cell. 2007 Dec; 18(12):4992-5003. View in: PubMed

  34. Werner M, Munro E, Glotzer M. Astral signals spatially bias cortical myosin recruitment to break symmetry and promote cytokinesis. Curr Biol. 2007 Aug 07; 17(15):1286-97. View in: PubMed

  35. Petronczki M, Glotzer M, Kraut N, Peters JM. Polo-like kinase 1 triggers the initiation of cytokinesis in human cells by promoting recruitment of the RhoGEF Ect2 to the central spindle. Dev Cell. 2007 May; 12(5):713-25. View in: PubMed

  36. Hizlan D, Mishima M, Tittmann P, Gross H, Glotzer M, Hoenger A. Structural analysis of the ZEN-4/CeMKLP1 motor domain and its interaction with microtubules. J Struct Biol. 2006 Jan; 153(1):73-84. View in: PubMed

  37. Piekny A, Werner M, Glotzer M. Cytokinesis: welcome to the Rho zone. Trends Cell Biol. 2005 Dec; 15(12):651-8. View in: PubMed

  38. Yüce O, Piekny A, Glotzer M. An ECT2-centralspindlin complex regulates the localization and function of RhoA. J Cell Biol. 2005 Aug 15; 170(4):571-82. View in: PubMed

  39. Guse A, Mishima M, Glotzer M. Phosphorylation of ZEN-4/MKLP1 by aurora B regulates completion of cytokinesis. Curr Biol. 2005 Apr 26; 15(8):778-86. View in: PubMed

  40. Glotzer M. The molecular requirements for cytokinesis. Science. 2005 Mar 18; 307(5716):1735-9. View in: PubMed

  41. Balasubramanian MK, Bi E, Glotzer M. Comparative analysis of cytokinesis in budding yeast, fission yeast and animal cells. Curr Biol. 2004 Sep 21; 14(18):R806-18. View in: PubMed

  42. Mishima M, Pavicic V, Grüneberg U, Nigg EA, Glotzer M. Cell cycle regulation of central spindle assembly. Nature. 2004 Aug 19; 430(7002):908-13. View in: PubMed

  43. Glotzer M. Cleavage furrow positioning. J Cell Biol. 2004 Feb 02; 164(3):347-51. View in: PubMed

  44. Glotzer M. Cytokinesis: progress on all fronts. Curr Opin Cell Biol. 2003 Dec; 15(6):684-90. View in: PubMed

  45. Mishima M, Glotzer M. Cytokinesis: a logical GAP. Curr Biol. 2003 Aug 05; 13(15):R589-91. View in: PubMed

  46. Romano A, Guse A, Krascenicova I, Schnabel H, Schnabel R, Glotzer M. CSC-1: a subunit of the Aurora B kinase complex that binds to the survivin-like protein BIR-1 and the incenp-like protein ICP-1. J Cell Biol. 2003 Apr 28; 161(2):229-36. View in: PubMed

  47. Schleiffer A, Kaitna S, Maurer-Stroh S, Glotzer M, Nasmyth K, Eisenhaber F. Kleisins: a superfamily of bacterial and eukaryotic SMC protein partners. Mol Cell. 2003 Mar; 11(3):571-5. View in: PubMed

  48. Dechant R, Glotzer M. Centrosome separation and central spindle assembly act in redundant pathways that regulate microtubule density and trigger cleavage furrow formation. Dev Cell. 2003 Mar; 4(3):333-44. View in: PubMed

  49. Macara IG, Baldarelli R, Field CM, Glotzer M, Hayashi Y, Hsu SC, Kennedy MB, Kinoshita M, Longtine M, Low C, Maltais LJ, McKenzie L, Mitchison TJ, Nishikawa T, Noda M, Petty EM, Peifer M, Pringle JR, Robinson PJ, Roth D, Russell SE, Stuhlmann H, Tanaka M, Tanaka T, Trimble WS, Ware J, Zeleznik-Le NJ, Zieger B. Mammalian septins nomenclature. Mol Biol Cell. 2002 Dec; 13(12):4111-3. View in: PubMed

  50. Mendoza M, Hyman AA, Glotzer M. GTP binding induces filament assembly of a recombinant septin. Curr Biol. 2002 Oct 29; 12(21):1858-63. View in: PubMed

  51. Gruneberg U, Glotzer M, Gartner A, Nigg EA. The CeCDC-14 phosphatase is required for cytokinesis in the Caenorhabditis elegans embryo. J Cell Biol. 2002 Sep 02; 158(5):901-14. View in: PubMed

  52. Glotzer M, Dechant R. Cytokinesis: regulated by destruction. Curr Biol. 2002 May 14; 12(10):R344-6. View in: PubMed

  53. Kaitna S, Pasierbek P, Jantsch M, Loidl J, Glotzer M. The aurora B kinase AIR-2 regulates kinetochores during mitosis and is required for separation of homologous Chromosomes during meiosis. Curr Biol. 2002 May 14; 12(10):798-812. View in: PubMed

  54. Kaitna S, Schnabel H, Schnabel R, Hyman AA, Glotzer M. A ubiquitin C-terminal hydrolase is required to maintain osmotic balance and execute actin-dependent processes in the early C. elegans embryo. J Cell Sci. 2002 Jun 01; 115(Pt 11):2293-302. View in: PubMed

  55. Mishima M, Kaitna S, Glotzer M. Central spindle assembly and cytokinesis require a kinesin-like protein/RhoGAP complex with microtubule bundling activity. Dev Cell. 2002 Jan; 2(1):41-54. View in: PubMed

  56. Siomos MF, Badrinath A, Pasierbek P, Livingstone D, White J, Glotzer M, Nasmyth K. Separase is required for chromosome segregation during meiosis I in Caenorhabditis elegans. Curr Biol. 2001 Nov 27; 11(23):1825-35. View in: PubMed

  57. Glotzer M. Animal cell cytokinesis. Annu Rev Cell Dev Biol. 2001; 17:351-86. View in: PubMed

  58. Kaitna S, Mendoza M, Jantsch-Plunger V, Glotzer M. Incenp and an aurora-like kinase form a complex essential for chromosome segregation and efficient completion of cytokinesis. Curr Biol. 2000 Oct 05; 10(19):1172-81. View in: PubMed

  59. Jantsch-Plunger V, Gönczy P, Romano A, Schnabel H, Hamill D, Schnabel R, Hyman AA, Glotzer M. CYK-4: A Rho family gtpase activating protein (GAP) required for central spindle formation and cytokinesis. J Cell Biol. 2000 Jun 26; 149(7):1391-404. View in: PubMed

  60. Jantsch-Plunger V, Glotzer M. Depletion of syntaxins in the early Caenorhabditis elegans embryo reveals a role for membrane fusion events in cytokinesis. Curr Biol. 1999 Jul 15; 9(14):738-45. View in: PubMed

  61. Glotzer M. Chromosome segregation: Samurai separation of Siamese sisters. Curr Biol. 1999 Jul 15; 9(14):R531-4. View in: PubMed

  62. Glotzer M. The mechanism and control of cytokinesis. Curr Opin Cell Biol. 1997 Dec; 9(6):815-23. View in: PubMed

  63. Wheatley SP, Hinchcliffe EH, Glotzer M, Hyman AA, Sluder G, Wang Yl. CDK1 inactivation regulates anaphase spindle dynamics and cytokinesis in vivo. J Cell Biol. 1997 Jul 28; 138(2):385-93. View in: PubMed

  64. Glotzer M. Cytokinesis. Curr Biol. 1997 May 01; 7(5):R274-6. View in: PubMed

  65. Glotzer JB, Saffrich R, Glotzer M, Ephrussi A. Cytoplasmic flows localize injected oskar RNA in Drosophila oocytes. Curr Biol. 1997 May 01; 7(5):326-37. View in: PubMed

  66. Drechsel DN, Hyman AA, Hall A, Glotzer M. A requirement for Rho and Cdc42 during cytokinesis in Xenopus embryos. Curr Biol. 1997 Jan 01; 7(1):12-23. View in: PubMed

  67. Glotzer M. Mitosis: don't get mad, get even. Curr Biol. 1996 Dec 01; 6(12):1592-4. View in: PubMed

  68. King RW, Glotzer M, Kirschner MW. Mutagenic analysis of the destruction signal of mitotic cyclins and structural characterization of ubiquitinated intermediates. Mol Biol Cell. 1996 Sep; 7(9):1343-57. View in: PubMed

  69. Glotzer M, Hyman AA. Cell polarity. The importance of being polar. Curr Biol. 1995 Oct 01; 5(10):1102-5. View in: PubMed

  70. Glotzer M. Cell cycle. The only way out of mitosis. Curr Biol. 1995 Sep 01; 5(9):970-2. View in: PubMed

  71. Holloway SL, Glotzer M, King RW, Murray AW. Anaphase is initiated by proteolysis rather than by the inactivation of maturation-promoting factor. Cell. 1993 Jul 02; 73(7):1393-402. View in: PubMed

  72. Jacobsson A, Stadler U, Glotzer MA, Kozak LP. Mitochondrial uncoupling protein from mouse brown fat. Molecular cloning, genetic mapping, and mRNA expression. J Biol Chem. 1985 Dec 25; 260(30):16250-4. View in: PubMed

  73. Solomon MJ, Glotzer M, Lee TH, Philippe M, Kirschner MW. Cyclin activation of p34cdc2. Cell. 1990 Nov 30; 63(5):1013-24. View in: PubMed

  74. Gautier J, Minshull J, Lohka M, Glotzer M, Hunt T, Maller JL. Cyclin is a component of maturation-promoting factor from Xenopus. Cell. 1990 Feb 09; 60(3):487-94. View in: PubMed

  75. Glotzer M, Murray AW, Kirschner MW. Cyclin is degraded by the ubiquitin pathway. Nature. 1991 Jan 10; 349(6305):132-8. View in: PubMed