Biochemical and biophysical research communications, 2007-02, Vol.353 (4), p.869-874
2007
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- Autor(en) / Beteiligte
- Titel
- Intracellular distribution of a speech/language disorder associated FOXP2 mutant
- Ist Teil von
- Biochemical and biophysical research communications, 2007-02, Vol.353 (4), p.869-874
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2007
- Quelle
- Access via ScienceDirect (Elsevier)
- Beschreibungen/Notizen
- 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, Zn 2+ 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0006-291XeISSN: 1090-2104DOI: 10.1016/j.bbrc.2006.12.130Titel-ID: cdi_osti_scitechconnect_20979804
- Format
- –
- Schlagworte
- 60 APPLIED LIFE SCIENCES, Amino Acid Sequence, Amino Acid Substitution, Animals, Axenfeld-Rieger anomaly, Binding Sites - genetics, Blotting, Western, Cell Line, CELL NUCLEI, Cell Nucleus - metabolism, Cercopithecus aethiops, COS Cells, CYTOPLASM, Cytoplasm - metabolism, Dimerization, Forkhead, Forkhead Transcription Factors - chemistry, Forkhead Transcription Factors - genetics, Forkhead Transcription Factors - metabolism, FOX, FOXC1, FOXE1/TTF2, FOXP2, GENES, Green Fluorescent Proteins - genetics, Green Fluorescent Proteins - metabolism, Humans, Importin, Intracellular Space - metabolism, Language Disorders - genetics, Language Disorders - metabolism, Language Disorders - pathology, Molecular Sequence Data, Mutant Proteins - chemistry, Mutant Proteins - genetics, Mutant Proteins - metabolism, MUTANTS, Mutation, MUTATIONS, NLS, PATHOGENESIS, PATIENTS, Polyglutamine, PROTEINS, Recombinant Fusion Proteins - genetics, Recombinant Fusion Proteins - metabolism, SENSE ORGANS, SENSE ORGANS DISEASES, Sequence Homology, Amino Acid, Spectrometry, Fluorescence, SPEECH, Speech Disorders - genetics, Speech Disorders - metabolism, Speech Disorders - pathology, Speech/language disorder, Transfection, ZINC IONS