DEVELOPMENT: Import Controls

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Science  05 Jan 2007:
Vol. 315, Issue 5808, pp. 18d-19d
DOI: 10.1126/science.315.5808.18d

The directed and controlled differentiation of cells is of critical importance for being able to use embryonic stem cells in a clinical setting. Yasuhara et al. have shown that a switch in a nuclear transport mechanism is involved in cell fate determination. For nuclear import, a protein with a nuclear localization signal (NLS) binds to the receptor importin-α, which in turn recruits importin-β to mediate translocation through the nuclear pore. They find that mouse embryonic stem (ES) cells express the subtype importin-α1, whereas cells that have differentiated into neurons express importin-α5. Experimental manipulation confirmed that neural differentiation can be enhanced by combining the down-regulation of importin-α1 with the overexpression of importin-α5. Hence, the switching of importin-α subtype triggers neural differentiation of ES cells. The authors propose a mechanism by which importin-α subtypes function in either the undifferentiated or differentiated state by controlling the selective import of transcription factors into the nucleus—Oct3/4 for the former and Brn2 with SOX2 in the latter—which adds yet another layer of regulation for cell fate specification, this one acting via the intracellular trafficking of transcription factors. — BAP

Nature Cell Biol. 10.1038/ncb1521 (2006).

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