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ORIGINAL ARTICLE
Temporal expression and mitochondrial localization of a Foxp2 isoform lacking the forkhead domain in developing Purkinje cells
Article first published online: 3 NOV 2011
DOI: 10.1111/j.1471-4159.2011.07524.x
© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry
Additional Information
How to Cite
Tanabe, Y., Fujiwara, Y., Matsuzaki, A., Fujita, E., Kasahara, T., Yuasa, S. and Momoi, T. (2012), Temporal expression and mitochondrial localization of a Foxp2 isoform lacking the forkhead domain in developing Purkinje cells. Journal of Neurochemistry, 122: 72–80. doi: 10.1111/j.1471-4159.2011.07524.x
Publication History
- Issue published online: 11 JUN 2012
- Article first published online: 3 NOV 2011
- Accepted manuscript online: 11 OCT 2011 01:53AM EST
- Received May 6, 2011; revised manuscript received September 8, 2011; accepted October 4, 2011.
Keywords:
- alternative splice product;
- cerebellum;
- Foxp2;
- mitochondria;
- Purkinje cell
J. Neurochem. (2012) 122, 72–80.
Abstract
FOXP2, a forkhead box-containing transcription factor, forms homo- or hetero-dimers with FOXP family members and localizes to the nucleus, while FOXP2(R553H), which contains a mutation related to speech/language disorders, features reduced DNA binding activity and both cytoplasmic and nuclear localization. In addition to being a loss-of-function mutation, it is possible that FOXP2(R553H) also may act as a gain-of-function mutation to inhibit the functions of FOXP2 isoforms including FOXP2Ex10+ lacking forkhead domain. Foxp2(R552H) knock-in mouse pups exhibit impaired ultrasonic vocalization and poor dendritic development in Purkinje cells. However, expressions of Foxp2 isoforms in the developing Purkinje are unclear. The appearance of ‘apical cytoplasmic swelling’ (mitochondria-rich regions that are the source of budding processes) correlates with dendritic development of Purkinje cells. In the present study, we focused on Foxp2 isoforms localizing to the apical cytoplasmic swelling and identified two isoforms lacking forkhead domain: Foxp2Ex12+ and Foxp2Ex15. They partly localized to the membrane fraction that includes mitochondria. Foxp2Ex12+ mainly localized to the apical cytoplasmic swelling in early developing Purkinje cells at the stellate stage (P2–P4). Mitochondrial localization of Foxp2Ex12+ in Purkinje cells was confirmed by immune-electron microscopic analysis. Foxp2Ex12+ may play a role in dendritic development in Purkinje cells.