A specific role for the TFIID subunit TAF4 and RanBPM in neural progenitor differentiation.
TAF4 is crucial for the activity of many transcription factors, including CREB, RAR and CSL/RBP-Jkappa, but the role for TAF4 in neural development is unknown. Embryonic cortical neural stem cells (NSC) showed strong expression of TAF4 that decreased during neuronal but not glial differentiation. In a protein-protein interaction screen, we identified the intracellular signaling factor RanBPM as a co-factor of TAF4. RanBPM co-localized with TAF4 in a subset of mitotic progenitors in vivo and endogenous TAF4 and RanBPM could be co-immunoprecipitated from NSC extracts. Interestingly, co-transfections of TAF4 and RanBPM led to a significant increase in the number of primary neurite processes but no increase in total neurite length, whereas RanBPM and a TAF4 isoform lacking the RanBPM-interacting domain exerted no significant effect. Our results demonstrate that temporally high expression levels of two factors considered to be relatively general in function can influence very specific events in neuronal differentiation.
Brunkhorst
Adrian
A
Center for Genomics and Bioinformatics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Karlén
Mattias
M
Shi
Jiaqi
J
Mikolajczyk
Monika
M
Nelson
Mark A
MA
Metsis
Madis
M
Hermanson
Ola
O
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics / Q000378:metabolism*; D035362:Transcription Factor TFIID / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D020931:ran GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D009687:Nuclear Proteins; C116005:Ran binding protein 9; C101882:TAF4 protein, human; C504204:TAF4 protein, rat; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D020931:ran GTP-Binding Protein