The Rho GTPase effector protein, mDia, inhibits the DNA binding ability of the transcription factor Pax6 and changes the pattern of neurite extension in cerebellar granule cells through its binding to Pax6.
mDia, one of the target proteins of the GTPase Rho, is known to be involved in cytoskeletal reorganization and cytokinesis. Here, we report that mDia enters the nucleus and binds to the transcription factor, Pax6. In cultured non-neuronal cells, overexpression of mDia with Pax6 causes redistribution of some Pax6 molecules from the nucleus to the cytosol and decreases Pax6 transcriptional activity. Because Pax6 functions in the early central nervous system morphogenesis, we also examined the effects of mDia on endogenous Pax6 localization and neurite extension in cerebellar granule cells. Here too, Pax6 was partially mislocalized to the cytosol, and its expression level was decreased by mDia overexpression. In addition, mDia overexpression in these cells led to increased neurite branching and length. These results strongly suggest that mDia influences Pax6-induced transcriptional activity and axonal pathfinding in a way opposite from ROCK (Rho kinase) and that it may act via Pax6 to modulate early neuronal development.
D016475:3T3 Cells; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology*; D003600:Cytosol / Q000378:metabolism; D005136:Eye Proteins; D000080865:Formins; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D020798:Two-Hybrid System Techniques; D054460:rho-Associated Kinases
D002352:Carrier Proteins; C491464:Diap1 protein, mouse; D005136:Eye Proteins; D000080865:Formins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D008156:Luciferases; D005982:Glutathione Transferase; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases