The regulation of dynein function in membrane movement by NudEL

  • Yen Ching Yang

    Student thesis: Unknown


    The accurate regulation of cytoplasmic dynein-1 (dynein) is very important since dynein performs multiple functions in cells. In interphase, dynein is responsible for the correct positioning of membrane organelles, such as the Golgi complex and lysosomes. Previous work suggests that dynein's accessory proteins NudEL/Nde1/LIS1¬ may be involved in regulating dynein-dependent organelle movement. This study focuses on how NudEL regulates dynein-driven membrane movement. By using various NudEL fragments, this work presents the first evidence that NudEL is involved in the regulation of dynein-driven ER movement in vitro. Moreover, the in vivo organelle positioning assays also indicate additional regulatory function of NudEL.NudEL fragment (1-157 aa) which contains both the dynein and LIS1 binding domains is sufficient to activate dynein-driven membrane movement, since NudEL1-157 aa activates ER motility in vitro and enhances clustering of the Golgi complex and lysosomes in the peri-nuclear region in vivo. On the other hand, NudEL 96-206 aa containing the LIS1 binding domain alone inhibits ER motility in vitro and causes scattering of the Golgi complex and lysosomes in vivo, indicating an inhibition of dynein-dependent organelle movement. The activation of dynein activity requires the recruitment of LIS1 to the dynein complex by NudEL, since NudEL 1-157 aa has strong binding affinity to both LIS1 and dynein whereas NudEL 96-206 aa binds to LIS1 but not dynein which suggests the sequestering of LIS1 from the dynein complex. Interestingly, NudEL 1-206 aa, which also contains both the dynein and LIS1 binding domains, causes the dispersal of the Golgi complex and lysosomes in vivo, but to a lesser extent than NudEL 96-206 aa. The putative NudEL regulatory domain (157 -242 aa, which contains various phosphorylation sits and is less conserved between NudEL and Nde1) in NudEL 1-206 aa may regulate the interaction of LIS1 and the dynein complex, since NudEL 1-206 aa has strong binding affinity to LIS1 and weak binding affinity to dynein. However, further work is needed to understand the exact mechanism by which this putative NudEL domain regulates dynein activity.
    Date of Award1 Aug 2014
    Original languageEnglish
    Awarding Institution
    • The University of Manchester
    SupervisorViki Allan (Supervisor) & Eileithyia Swanton (Supervisor)


    • Organelle positioning
    • ER movement
    • LIS1
    • Ndel1
    • Dynein
    • Motor Protein
    • NudEL

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