Exportin 4 mediates a novel nuclear import pathway for Sox family transcription factors.
SRY and other Sox-type transcription factors are important developmental regulators with various implications in human disease. In this study, we identified Exp4 (exportin 4) as an interaction partner of Sox2 in mouse embryonic stem cells and neural progenitors. We show that, besides its established function in nuclear export, Exp4 acts as a bona fide nuclear import receptor for Sox2 and SRY. Thus, Exp4 is an example of a nuclear transport receptor carrying distinct cargoes into different directions. In contrast to a published study, we observed that the import activity of Imp-alpha (importin-a) isoforms toward Sox2 is negligible. Instead, we found that Imp9 and the Imp-beta/7 heterodimer mediate nuclear import of Sox2 in parallel to Exp4. Import signals for the three pathways overlap and include conserved residues in the Sox2 high-mobility group (HMG) box domain that are also critical for DNA binding. This suggests that nuclear import of Sox proteins is facilitated by several parallel import pathways.
Department of Pediatric Surgery, Erasmus Medical Center, Rotterdam, Netherlands.
Cristina
C
Gontan
Thomas
T
Güttler
Erik
E
Engelen
Jeroen
J
Demmers
Maarten
M
Fornerod
Frank G
FG
Grosveld
Dick
D
Tibboel
Dirk
D
Görlich
Raymond A
RA
Poot
Robbert J
RJ
Rottier
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D024742:HMG-Box Domains; D028884:Karyopherins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D021382:Protein Sorting Signals; D055747:SOX Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D051876:Sex-Determining Region Y Protein / Q000378:metabolism
D028884:Karyopherins; D021382:Protein Sorting Signals; D055747:SOX Transcription Factors; D055748:SOXB1 Transcription Factors; D051876:Sex-Determining Region Y Protein; C527783:Sox2 protein, mouse; C497746:Sry protein, mouse; C485892:Xpo4 protein, mouse