Mechanisms of Mitosis

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Our team studies the mechanisms that regulate proper chromosome separation during mitosis. This requires correct attachment of the chromosomes (blue) to the mitotic spindle (red), via their kinetochores (yellow).

The mitotic spindle consists of microtubules (MTs) that are hollow tubular structures assembled from tubulin dimers a and b. MTs are polarized: they are nucleated from their minus end through a g-tubulin guide that is located throughout the spindle, with the highest concentration at centrosomes. This is why the centrosome is often represented as the main organizing centre of MTs. However, MT nucleation is not exclusively centrosome-dependent. Indeed, in mitosis, nucleation also occurs around chromosomes, due to the concentration of RANGTP activity that releases spindle assembly factors. Moreover, there is also a mechanism of MT nucleation from pre-existing MTs (branching) that is dependent on the augmin complex.

MTs also harbour on their peptide chains a combination of covalent post-translational modifications (PTMs) that play an important role in differentiated cells. New mitotic functions of microtubule PTMs are progressively identified and they could modulate the mitotic spindle plasticity during its evolution by specifying spatially and temporally the recruitment of microtubule-associated proteins (MAPs).

Many MAPs are known, but their precise functions are not well understood. In our team, we develop simplified systems to study nucleated MTs separately in isolated nucleation centres (chromosomes, kinetochores, centrosomes, pre-existing MTs) and/or modified by a single type of post-translational modification (acetylation, glutamylation, detyrosination). Together, these data allow us to better dissect, and thus to better understand the regulation of MT dynamics within the mitotic spindle.

 

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Nathalie Morin

Members of the team

  • Claude DELSERT
    (Staff Scientist) +33 (0)4 34 35 95 90
  • Nathalie MORIN Group Leader
    (Staff Scientist) +33 (0)4 34 35 95 52
  • Gabriel RABEHARIVELO
    (Research Assistant) +33 (0)4 34 35 95 90
  • Juliette VAN DIJK
    (Staff Scientist) +33 (0)4 34 35 95 52
    • 2018

      Microtubule polyglutamylation and acetylation drive microtubule dynamics critical for platelet formation.

      van Dijk J, Bompard G, Cau J, Kunishima S, Rabeharivelo G, Mateos-Langerak J, Cazevieille C, Cavelier P, Boizet-Bonhoure B, Delsert[...]

      BMC Biol. 16(1):116. Pubmed

    • 2017

      Initiation of DNA replication requires actin dynamics and formin activity.

      Parisis N, Krasinska L, Harker B, Urbach S, Rossignol M, Camasses A, Dewar J, Morin N, Fisher D.

      EMBO J. pii: e201796585. Pubmed

    • 2017

      Early gametogenesis in the Pacific oyster: new insights using stem cell and mitotic markers.

      Cavelier P, Cau J, Morin N, Delsert C.

      J Exp Biol. pii: jeb.167734. Pubmed

    • 2017

      Heterogeneity in sarcoma cell lines reveals enhanced motility of tetraploid versus diploid cells.

      Jemaà M, Abdallah S, Lledo G, Perot G, Lesluyes T, Teyssier C, Roux P, van Dijk J, Chibon F, Abrieu[...]

      Oncotarget. 14291 Pubmed

    • 2017

      Bub1 targeting to centromeres is sufficient for Sgo1 recruitment in the absence of kinetochores.

      Williams SJ, Abrieu A, Losada A.

      Chromosoma. Pubmed

    • 2016

      Whole-genome duplication increases tumor cell sensitivity to MPS1 inhibition.

      Jemaà M, Manic G, Lledo G, Lissa D, Reynes C, Morin N, Chibon F, Sistigu A, Castedo M, Vitale I,[...]

      Oncotarget. 7:885-901. Pubmed

    • 2015

      Binding of Kif23-iso1/CHO1 to 14-3-3 is regulated by sequential phosphorylations at two LATS kinase consensus sites.

      Fesquet D, De Bettignies G, Bellis M, Espeut J, Devault A.

      PLoS One. 10:e0117857. Pubmed

    • 2015

      Natural Loss of Mps1 Kinase in Nematodes Uncovers a Role for Polo-like Kinase 1 in Spindle Checkpoint Initiation.

      Espeut J, Lara-Gonzalez P, Sassine M, Shiau AK, Desai A, Abrieu A.

      Cell Rep. 12:58-65. Pubmed

    • 2015

      Dynamic localization of Mps1 kinase to kinetochores is essential for accurate spindle microtubule attachment.

      Dou Z, Liu X, Wang W, Zhu T, Wang X, Xu L, Abrieu A, Fu C, Hill DL, Yao X.

      Proc Natl Acad Sci U S A. 112:E4546-55. Pubmed

    • 2015

      Characterisation of polyglutamylases in trypanosomatids.

      Casanova M, de Monbrison F, van Dijk J, Janke C, Pagès M, Bastien P.

      Int J Parasitol. 45(2-3):121-32. Pubmed

    • 2014

      Adult somatic progenitor cells and hematopoiesis in oysters.

      Jemaà M, Morin N, Cavelier P, Cau J, Strub JM, Delsert C.

      J Exp Biol. 217(Pt 17):3067-77. Pubmed

    • 2013

      P21-activated kinase 4 (PAK4) is required for metaphase spindle positioning and anchoring.

      Bompard G, Rabeharivelo G, Cau J, Abrieu A, Delsert C, Morin N.

      Oncogene. 32(7):910-9. Pubmed

    • 2012

      p21-activated kinase 4 regulates mitotic spindle positioning and orientation.

      Bompard G, Morin N.

      Bioarchitecture. 2(4):130-3. Pubmed

    • 2012

      CDK-dependent potentiation of MPS1 kinase activity is essential to the mitotic checkpoint.

      Morin V, Prieto S, Melines S, Hem S, Rossignol M, Lorca T, Espeut J, Morin N, Abrieu A.

      Curr Biol. 22(4):289-95. Pubmed

    • 2011

      UA62784 Is a cytotoxic inhibitor of microtubules, not CENP-E.

      Tcherniuk S, Deshayes S, Sarli V, Divita G, Abrieu A.

      Chem Biol. 18(5):631-41. Pubmed

    • 2011

      Activity of the RhoU/Wrch1 GTPase is critical for cranial neural crest cell migration.

      Fort P, Guémar L, Vignal E, Morin N, Notarnicola C, de Santa Barbara P, Faure S.

      Dev Biol. 350(2):451-63. Pubmed

    • 2010

      Probing CENP-E function in chromosome dynamics using small molecule inhibitor syntelin.

      Ding X, Yan F, Yao P, Yang Z, Wan W, Wang X, Liu J, Gao X, Abrieu A, Zhu T,[...]

      Cell Res. 20(12):1386-9. Pubmed

    • 2010

      Subgroup II PAK-mediated phosphorylation regulates Ran activity during mitosis.

      Bompard G, Rabeharivelo G, Frank M, Cau J, Delsert C, Morin N.

      J Cell Biol. 190(5):807-22. Pubmed

    • 2010

      A family of protein-deglutamylating enzymes associated with neurodegeneration.

      Rogowski K, van Dijk J, Magiera MM, Bosc C, Deloulme JC, Bosson A, Peris L, Gold ND, Lacroix B, Bosch[...]

      Cell. 2010 143(4):564-78. Pubmed

    • 2010

      Tubulin polyglutamylation stimulates spastin-mediated microtubule severing.

      Lacroix B, van Dijk J, Gold ND, Guizetti J, Aldrian-Herrada G, Rogowski K, Gerlich DW, Janke C.

      J Cell Biol. 189(6):945-54. Pubmed

    • 2008

      Phosphorylation relieves autoinhibition of the kinetochore motor Cenp-E.

      Espeut J, Gaussen A, Bieling P, Morin V, Prieto S, Fesquet D, Surrey T, Abrieu A.

      Mol Cell. 29(5):637-43. Pubmed