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Nat Commun. 2018 Jun 13;9(1):2330. doi: 10.1038/s41467-018-04706-7.

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

Author information

1
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028, Barcelona, Spain.
2
Molecular Biology Institute of Barcelona (IBMB-CSIC), 08028, Barcelona, Spain.
3
Department of Cell Biology, Physiology and Immunology, Faculty of Biology, Institute of Neurosciences, University of Barcelona, 08028, Barcelona, Spain.
4
Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), ISCIII, 28031, Madrid, Spain.
5
Vall d'Hebron Institute of Research, 08035, Barcelona, Spain.
6
Institucio Catalana de Recerca i Estudis Avancats (ICREA), 08010, Barcelona, Spain.
7
Centre de Recherche en Biologie Cellulaire de Montpellier, CRBM-CNRS, UMR5237 Montpellier, 1919 Route de Mende, 34293, Montpellier, France.
8
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028, Barcelona, Spain. jens.luders@irbbarcelona.org.

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.

PMID:
29899413
PMCID:
PMC5997995
DOI:
10.1038/s41467-018-04706-7
[Indexed for MEDLINE]
Free PMC Article

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