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Regulation of neuronal morphogenesis by 14-3-3epsilon (Ywhae) via the microtubule binding protein, doublecortin
Journal article   Open access   Peer reviewed

Regulation of neuronal morphogenesis by 14-3-3epsilon (Ywhae) via the microtubule binding protein, doublecortin

Brett Cornell, Tomoka Wachi, Vladimir Zhukarev and Kazuhito Toyo-Oka
Human molecular genetics, v 25(20), pp 4405-4418
15 Oct 2016
DOI: https://doi.org/10.1093/hmg/ddw270
PMID: 28173130
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1093/hmg/ddw270View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  Open

Abstract

14-3-3 Proteins - genetics 14-3-3 Proteins - metabolism Animals Autism Spectrum Disorder - genetics Carrier Proteins Chromosome Deletion Gene Duplication Humans Intellectual Disability - genetics Mice Mice, Inbred ICR Microtubule-Associated Proteins - genetics Microtubule-Associated Proteins - metabolism Microtubules - metabolism Morphogenesis Neurites - metabolism Neurons - metabolism Neuropeptides - genetics Neuropeptides - metabolism Protein Binding
17p13.3 microduplication syndrome is a newly identified genetic disorder characterized by duplications in the 17p13.3 chromosome locus, resulting in a variety of disorders including autism spectrum disorder (ASD). Importantly, a minimum duplication region has been defined, and this region exclusively contains the gene encoding 14-3-3ε. Furthermore, duplication of this minimum region is strongly associated with the appearance of ASD in human patients, thus implicating the overexpression of 14-3-3ε in ASD. Using in vitro and in vivo techniques, we have found that 14-3-3ε binds to the microtubule binding protein doublecortin preventing its degradation. We also found that 14-3-3ε overexpression disrupts neurite formation by preventing the invasion of microtubules into primitive neurites, which can be rescued by the knockdown of doublecortin. To analyse the function of 14-3-3ε in neurite formation, we used 14-3-3ε flox mice and found that 14-3-3ε deficiency results in an increase in neurite formation. Our findings provide the first evidence of cellular pathology in 17p13.3 microduplication syndrome.

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Web of Science research areas
Biochemistry & Molecular Biology
Genetics & Heredity
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