Phosphorylation of β-Tubulin by the Down Syndrome Kinase, Minibrain/DYRK1a, Regulates Microtubule Dynamics and Dendrite Morphogenesis

Kassandra M. Ori-McKenney, Richard Mckenney, Hector H. Huang, Tun Li, Shan Meltzer, Lily Yeh Jan, Ronald D. Vale, Arun P. Wiita, Yuh Nung Jan

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Dendritic arborization patterns are consistent anatomical correlates of genetic disorders such as Down syndrome (DS) and autism spectrum disorders (ASDs). In a screen for abnormal dendrite development, we identified Minibrain (MNB)/DYRK1a, a kinase implicated in DS and ASDs, as a regulator of the microtubule cytoskeleton. We show that MNB is necessary to establish the length and cytoskeletal composition of terminal dendrites by controlling microtubule growth. Altering MNB levels disrupts dendrite morphology and perturbs neuronal electrophysiological activity, resulting in larval mechanosensation defects. Using in vivo and in vitro approaches, we uncover a molecular pathway whereby direct phosphorylation of β-tubulin by MNB inhibits tubulin polymerization, a function that is conserved for mammalian DYRK1a. Our results demonstrate that phosphoregulation of microtubule dynamics by MNB/DYRK1a is critical for dendritic patterning and neuronal function, revealing a previously unidentified mode of posttranslational microtubule regulation in neurons and uncovering a conserved pathway for a DS- and ASD-associated kinase. Ori-McKenney et al. identify a conserved mechanism for a Down syndrome critical kinase in regulating microtubule growth during neuronal development. MNB/DYRK1a inhibits microtubule polymerization by phosphorylating tubulin, a pathway that contributes to proper dendritic patterning and overall neuronal function.

Original languageEnglish (US)
Pages (from-to)551-563
Number of pages13
JournalNeuron
Volume90
Issue number3
DOIs
StatePublished - May 4 2016

ASJC Scopus subject areas

  • Neuroscience(all)

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    Ori-McKenney, K. M., Mckenney, R., Huang, H. H., Li, T., Meltzer, S., Jan, L. Y., Vale, R. D., Wiita, A. P., & Jan, Y. N. (2016). Phosphorylation of β-Tubulin by the Down Syndrome Kinase, Minibrain/DYRK1a, Regulates Microtubule Dynamics and Dendrite Morphogenesis. Neuron, 90(3), 551-563. https://doi.org/10.1016/j.neuron.2016.03.027