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NEK7 regulates dendrite morphogenesis in neurons via Eg5-dependent microtubule stabilization

Author

Listed:
  • Francisco Freixo

    (The Barcelona Institute of Science and Technology)

  • Paula Martinez Delgado

    (Molecular Biology Institute of Barcelona (IBMB-CSIC))

  • Yasmina Manso

    (University of Barcelona
    ISCIII
    Vall d’Hebron Institute of Research
    Institucio Catalana de Recerca i Estudis Avancats (ICREA))

  • Carlos Sánchez-Huertas

    (The Barcelona Institute of Science and Technology
    UMR5237 Montpellier)

  • Cristina Lacasa

    (The Barcelona Institute of Science and Technology)

  • Eduardo Soriano

    (University of Barcelona
    ISCIII
    Vall d’Hebron Institute of Research
    Institucio Catalana de Recerca i Estudis Avancats (ICREA))

  • Joan Roig

    (Molecular Biology Institute of Barcelona (IBMB-CSIC))

  • Jens Lüders

    (The Barcelona Institute of Science and Technology)

Abstract

Organization of microtubules into ordered arrays is best understood in mitotic systems, but remains poorly characterized in postmitotic cells such as neurons. By analyzing the cycling cell microtubule cytoskeleton proteome through expression profiling and targeted RNAi screening for candidates with roles in neurons, we have identified the mitotic kinase NEK7. We show that NEK7 regulates dendrite morphogenesis in vitro and in vivo. NEK7 kinase activity is required for dendrite growth and branching, as well as spine formation and morphology. NEK7 regulates these processes in part through phosphorylation of the kinesin Eg5/KIF11, promoting its accumulation on microtubules in distal dendrites. Here, Eg5 limits retrograde microtubule polymerization, which is inhibitory to dendrite growth and branching. Eg5 exerts this effect through microtubule stabilization, independent of its motor activity. This work establishes NEK7 as a general regulator of the microtubule cytoskeleton, controlling essential processes in both mitotic cells and postmitotic neurons.

Suggested Citation

  • Francisco Freixo & Paula Martinez Delgado & Yasmina Manso & Carlos Sánchez-Huertas & Cristina Lacasa & Eduardo Soriano & Joan Roig & Jens Lüders, 2018. "NEK7 regulates dendrite morphogenesis in neurons via Eg5-dependent microtubule stabilization," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04706-7
    DOI: 10.1038/s41467-018-04706-7
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