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

Francisco Freixo, Paula Martinez Delgado, Yasmina Manso, Carlos Sánchez-Huertas, Cristina Lacasa, Eduardo Soriano, Joan Roig and Jens Lüders ()
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Francisco Freixo: The Barcelona Institute of Science and Technology
Paula Martinez Delgado: Molecular Biology Institute of Barcelona (IBMB-CSIC)
Yasmina Manso: University of Barcelona
Carlos Sánchez-Huertas: The Barcelona Institute of Science and Technology
Cristina Lacasa: The Barcelona Institute of Science and Technology
Eduardo Soriano: University of Barcelona
Joan Roig: Molecular Biology Institute of Barcelona (IBMB-CSIC)
Jens Lüders: The Barcelona Institute of Science and Technology

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04706-7

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