Intracellular distribution of a speech/language disorder associated FOXP2 mutant
- Divisions of Development and Differentiation, Department of Human Inherited Metabolic Disease, National Institute of Neuroscience, Ogawahigashi-machi 4-1-1, Kodaira, Tokyo 187-8502 (Japan)
- Department of Pediatrics, Jichi Medical University, Yakushiji 3311-1, Shimotsukeshi, Tochigi 329-0498 (Japan)
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{sup 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 {alpha} and {beta}). 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.
- OSTI ID:
- 20979804
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 353, Issue 4; Other Information: DOI: 10.1016/j.bbrc.2006.12.130; PII: S0006-291X(06)02719-7; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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