Characterisation of ALADIN’s function during cell division

  • Sara Carvalhal

    Student thesis: Doctoral ThesisDoctor of Philosophy

    Abstract

    Cell division relies on many steps, precisely synchronised, to ensure the fidelity of chromosome segregation. To achieve such complex and multiple functions, cells have evolved mechanisms by which one protein can participate in numerous events on the cell life. Over the past few years, an increasing number of functions have been assigned to the proteins of the nuclear pore complex (NPC) also called nucleoporins. NPCs are large complexes studded in the nuclear envelope, which control the nucleocytoplasmic transport. It is now known that nucleoporins participate in spindle assembly, kinetochore organisation, spindle assembly checkpoint, and all processes important for genome integrity maintenance. This work demonstrates that the nucleoporin ALADIN participates in mitosis, meiosis and in cilia. In both mitosis and meiosis, ALADIN is important for proper spindle assembly. In mitosis, it was also discovered that ALADIN is a novel factor in the spatial regulation of the mitotic regulator Aurora A kinase. Without ALADIN, active Aurora A spreads from centrosomes onto spindle microtubules, which affects the distribution of a subset of microtubule regulators and slows spindle assembly and chromosome alignment. Interestingly, mutations in ALADIN causes triple A syndrome and some of the mitotic phenotypes observed after ALADIN depletion also occur in cells from triple A syndrome patients. In meiosis, ALADIN contributes to trigger the resumption of meiosis in female mouse. Impairment of ALADIN from mouse oocyte slows spindle assembly, migration and reduces oocytes ability to extrude polar bodies during meiosis I, which concomitantly affects the robustness of oocyte maturation and impairs mouse embryo development. Nucleoporins were also found at the base of the cilia, a centriole-derived organelle that participates in differentiation, migration, cell growth from development to adulthood. Here it is shown that ALADIN is also localised at the base of the cilia. With this work, new ALADIN’s functions have been identified across cell division, as well as uncovered an unexpected relation between triple A syndrome and cell division.
    Date of Award2015
    LanguageEnglish
    Awarding Institution
    • University of Dundee
    Add any sponsors of the thesis researchWellcome Trust & Biotechnology and Biological Sciences Research Council
    SupervisorEric Griffis (Supervisor)

    Keywords

    • Cell cycle
    • Cell division
    • Mitosis
    • Meiosis
    • ALADIN
    • Nucleoporin

    Cite this

    Characterisation of ALADIN’s function during cell division
    Carvalhal, S. (Author). 2015

    Student thesis: Doctoral ThesisDoctor of Philosophy