Huntingtin Is Required for Mitotic Spindle Orientation and Mammalian Neurogenesis

Juliette D. Godin, Kelly Colombo, Maria Molina-Calavita, Guy Keryer, Diana Zala, Béé Edicte C. Charrin, Paula Dietrich, Marie Laure Volvert, François Guillemot, Ioannis Dragatsis, Yohanns Bellaiche, Frédéric Saudou, Laurent Nguyen, Sandrine Humbert

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

Huntingtin is the protein mutated in Huntington's disease, a devastating neurodegenerative disorder. We demonstrate here that huntingtin is essential to control mitosis. Huntingtin is localized at spindle poles during mitosis. RNAi-mediated silencing of huntingtin in cells disrupts spindle orientation by mislocalizing the p150. Glued subunit of dynactin, dynein, and the large nuclear mitotic apparatus NuMA protein. This leads to increased apoptosis following mitosis of adherent cells in vitro. In vivo inactivation of huntingtin by RNAi or by ablation of the Hdh gene affects spindle orientation and cell fate of cortical progenitors of the ventricular zone in mouse embryos. This function is conserved in Drosophila, the specific disruption of Drosophila huntingtin in neuroblast precursors leading to spindle misorientation. Moreover, Drosophila huntingtin restores spindle misorientation in mammalian cells. These findings reveal an unexpected role for huntingtin in dividing cells, with potential important implications in health and disease.

Original languageEnglish (US)
Pages (from-to)392-406
Number of pages15
JournalNeuron
Volume67
Issue number3
DOIs
StatePublished - Aug 1 2010

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Spindle Apparatus
Neurogenesis
Mitosis
Drosophila
RNA Interference
Spindle Poles
Dyneins
Huntington Disease
Neurodegenerative Diseases
Embryonic Structures
Apoptosis
Health
Genes
Proteins

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Godin, J. D., Colombo, K., Molina-Calavita, M., Keryer, G., Zala, D., Charrin, B. E. C., ... Humbert, S. (2010). Huntingtin Is Required for Mitotic Spindle Orientation and Mammalian Neurogenesis. Neuron, 67(3), 392-406. https://doi.org/10.1016/j.neuron.2010.06.027

Huntingtin Is Required for Mitotic Spindle Orientation and Mammalian Neurogenesis. / Godin, Juliette D.; Colombo, Kelly; Molina-Calavita, Maria; Keryer, Guy; Zala, Diana; Charrin, Béé Edicte C.; Dietrich, Paula; Volvert, Marie Laure; Guillemot, François; Dragatsis, Ioannis; Bellaiche, Yohanns; Saudou, Frédéric; Nguyen, Laurent; Humbert, Sandrine.

In: Neuron, Vol. 67, No. 3, 01.08.2010, p. 392-406.

Research output: Contribution to journalArticle

Godin, JD, Colombo, K, Molina-Calavita, M, Keryer, G, Zala, D, Charrin, BEC, Dietrich, P, Volvert, ML, Guillemot, F, Dragatsis, I, Bellaiche, Y, Saudou, F, Nguyen, L & Humbert, S 2010, 'Huntingtin Is Required for Mitotic Spindle Orientation and Mammalian Neurogenesis', Neuron, vol. 67, no. 3, pp. 392-406. https://doi.org/10.1016/j.neuron.2010.06.027
Godin JD, Colombo K, Molina-Calavita M, Keryer G, Zala D, Charrin BEC et al. Huntingtin Is Required for Mitotic Spindle Orientation and Mammalian Neurogenesis. Neuron. 2010 Aug 1;67(3):392-406. https://doi.org/10.1016/j.neuron.2010.06.027
Godin, Juliette D. ; Colombo, Kelly ; Molina-Calavita, Maria ; Keryer, Guy ; Zala, Diana ; Charrin, Béé Edicte C. ; Dietrich, Paula ; Volvert, Marie Laure ; Guillemot, François ; Dragatsis, Ioannis ; Bellaiche, Yohanns ; Saudou, Frédéric ; Nguyen, Laurent ; Humbert, Sandrine. / Huntingtin Is Required for Mitotic Spindle Orientation and Mammalian Neurogenesis. In: Neuron. 2010 ; Vol. 67, No. 3. pp. 392-406.
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