Intracellular distribution of a speech/language disorder associated FOXP2 mutant

Akifumi Mizutani, Ayumi Matsuzaki, Mariko Y. Momoi, Eriko Fujita, Yuko Tanabe, Takashi Momoi

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)


Although a mutation (R553H) in the forkhead box (FOX)P2 gene is associated with speech/language disorder, little is known about the function of FOXP2 or its relevance to this disorder. In the present study, we identify the forkhead nuclear localization domains that contribute to the cellular distribution of FOXP2. Nuclear localization of FOXP2 depended on two distally separated nuclear localization signals in the forkhead domain. A truncated version of FOXP2 lacking the leu-zip, Zn2+ finger, and forkhead domains that was observed in another patient with speech abnormalities demonstrated an aggregated cytoplasmic localization. Furthermore, FOXP2 (R553H) mainly exhibited a cytoplasmic localization despite retaining interactions with nuclear transport proteins (importin α and β). Interestingly, wild type FOXP2 promoted the transport of FOXP2 (R553H) into the nucleus. Mutant and wild type FOXP2 heterodimers in the nucleus or FOXP2 R553H in the cytoplasm may underlie the pathogenesis of the autosomal dominant speech/language disorder.

Original languageEnglish
Pages (from-to)869-874
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number4
Publication statusPublished - Feb 23 2007


  • Axenfeld-Rieger anomaly
  • FOX
  • FOXC1
  • FOXE1/TTF2
  • FOXP2
  • Forkhead
  • Importin
  • NLS
  • Polyglutamine
  • Speech/language disorder

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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