Regulation of cytoskeleton

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Asymmetric cell division is the main mode of division of stem cells and plays a central role in generating cell diversity during development. Indeed, during asymmetric cell division of polarized cells, biomolecules are asymmetrically segregated between daughter cells. The position of the mitotic spindle within the cell determines whether the cell will divide symmetrically or asymmetrically. Spindle positioning, in turn, depends on the interaction of astral microtubules (cMTs) with cortical factors. A complex network of proteins, such as non-motor microtubule-associated proteins (plus-end tracking proteins, +TIPs), kinesins, dynein and actin-interacting proteins, are involved in these interactions.
Budding yeast also divides asymmetrically and is used as a model organism to study asymmetric cell division. Spindle positioning in yeast depends on two genetically identified pathways: i) the dynein pathway that includes complexes of the microtubule-dependent motor dynein, and ii) the Kar9 pathway. Kar9 is the yeast functional equivalent of the Adenomatous Polyposis Coli (APC) tumour suppressor, a protein with a central role in spindle positioning from Drosophila to mammals. Dynein, Kar9 and APC homologues are universal mediators of spindle positioning during eukaryotic asymmetric division, but their regulation is poorly understood.

In the laboratory, we explore how cell cycle regulators modulate the temporal activation and dynamics of dynein and Kar9 complexes during spindle positioning in budding yeast. During their transport along microtubules and interactions with cortical proteins, these factors form highly dynamic protein complexes. Cyclin-dependent kinases control both the formation of these complexes and the coordination of their activity with other cytoskeletal events, such as chromosome segregation and cytokinesis. To understand the regulation of Kar9 and dynein complexes we use genetics to study their interactions. Using protein biochemistry, we analyse the Kar9/dynein complex composition and phosphorylation. Finally, we investigate complex dynamics in living yeast cells by time-lapse fluorescence imaging.

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Dimitris Liakopoulos

Members of the team

  • Ariane ABRIEU
    (Staff Scientist) +33 (0)4 34 35 96 43
  • Florence GAVEN
    (Research Assistant) +33 (0)4 34 35 95 67
  • Paul LAMBEY
    (PhD Student) +33 (0)4 34 35 9
  • Dimitris LIAKOPOULOS Group Leader
    (Staff Scientist) +33 (0)4 34 35 95 67
  • Didier PORTRAN
    (Staff Scientist) +33 (0)4 34 35 96 43
    • 2019

      How Does SUMO Participate in Spindle Organization?

      Abrieu A, Liakopoulos D.

      Cells. 8(8). Pubmed

    • 2019

      Lattice defects induce microtubule self-renewal

      Laura Schaedel, Sarah Triclin, Denis Chrétien, Ariane Abrieu, Charlotte Aumeier, Jérémie Gaillard, Laurent Blanchoin, Manuel Théry & Karin John

      Nature Physicsvolume 15, pages830–838 Pubmed

    • 2018

      An E2-ubiquitin thioester-driven approach to identify substrates modified with ubiquitin and ubiquitin-like molecules.

      Bakos G, Yu L, Gak IA, Roumeliotis TI, Liakopoulos D, Choudhary JS, Mansfeld J.

      Nat Commun. 9(1):4776. Pubmed

    • 2016

      Kar9 controls the nucleocytoplasmic distribution of yeast EB1.

      J. Schweiggert, D. Panigada, AN. Tan, D. Liakopoulos

      Cell Cycle, 15 : 2860-2866. Pubmed

    • 2016

      Regulation of a Spindle Positioning Factor at Kinetochores by SUMO-Targeted Ubiquitin Ligases.

      Schweiggert J, Stevermann L, Panigada D, Kammerer D, Liakopoulos D.

      Dev Cell. 36:415-27. Pubmed

    • 2015

      Kinesin Kip2 enhances microtubule growth in vitro through length-dependent feedback on polymerization and catastrophe.

      Hibbel A, Bogdanova A, Mahamdeh M, Jannasch A, Storch M, Schäffer E, Liakopoulos D, Howard J.

      Elife. 4: e10542. Pubmed

    • 2013

      An auxiliary, membrane-based mechanism for nuclear migration in budding yeast.

      Kirchenbauer M, Liakopoulos D.

      Mol Biol Cell. 24(9):1434-43. Pubmed

    • 2010

      Ubiquitylation regulates interactions of astral microtubules with the cleavage apparatus.

      Kammerer D, Stevermann L, Liakopoulos D.

      Curr Biol. 20(14):1233-43. Pubmed

    • 2010

      Arp1, an actin-related protein, in Plasmodium berghei.

      Siden-Kiamos I, Schüler H, Liakopoulos D, Louis C.

      Mol Biochem Parasitol. 173(2):88-96. Pubmed

    • 2008

      Regulation of mitotic spindle asymmetry by SUMO and the spindle-assembly checkpoint in yeast.

      Leisner C, Kammerer D, Denoth A, Britschi M, Barral Y, Liakopoulos D.

      Curr Biol. 18(16):1249-55. Pubmed