STRA8 shuttles between nucleus and cytoplasm and displays transcriptional activity.
Stra8 (stimulated by retinoic acid 8) encodes a protein crucial for mammalian germ cells entering into premeiotic stages. Here, to elucidate the still unknown STRA8 molecular functions, we studied the cellular localization of the protein in several cell types, including premeiotic mouse germ cells and stem cell lines. We reported distinct STRA8 localization in germ and stem cell types and a heterogeneous protein distribution in the cytoplasm and nucleus of such cells suggesting that the protein can shuttle between these two compartments. Moreover, we identified specific protein motifs determining its nuclear import/export. Furthermore, we demonstrated that in transfected cell lines the nuclear import of STRA8 is an active process depending on an N-terminal basic nuclear localization signal. Moreover, its nuclear export is mainly mediated by the Exportin1 (XPO1) recognition of a nuclear export signal. Significantly, we also demonstrated that STRA8 associates with DNA and possesses transcriptional activity. These observations strongly suggest that STRA8 can exert important functions in the nucleus rather than in the cytoplasm as believed previously, likely depending on the cell type and regulated by its nuclear-cytoplasmic shuttling.
Tedesco
Marianna
M
Department of Public Health and Cell Biology, University of Rome Tor Vergata, 00173 Rome, Italy.
La Sala
Gina
G
Barbagallo
Federica
F
De Felici
Massimo
M
Farini
Donatella
D
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism*; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism; D008540:Meiosis / Q000502:physiology; D051379:Mice; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D000097606:Exportin 1 Protein
D048868:Adaptor Proteins, Signal Transducing; D004247:DNA; D028884:Karyopherins; D019913:Nuclear Localization Signals; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein; C102019:Stra8 protein, mouse