Nuclear translocation of the SRF co-activator MAL in cortical neurons: role of RhoA signalling.
Although it is well established that RhoA signaling pathways play key roles in regulating neuronal morphology, their involvement in other aspects of neuronal function has received little attention. Recent studies have elucidated a novel intracellular signaling pathway used by RhoA to elicit activation of serum response factor (SRF)-mediated transcription. In this pathway, activation of RhoA triggers nuclear translocation of the SRF co-activator, megakaryocytic acute leukemia (MAL). In assessing whether RhoA regulates transcription in neurons via this pathway, we have found that a constitutively active form of Tech (transcript-enriched in cortex and hippocampus), a RhoA guanine nucleotide exchange factor (GEF) that is expressed in forebrain neurons, stimulates SRF reporter activity in extracts of primary cortical cultures and induces nuclear translocation of MAL in cortical neurons. Both of these responses appear to be mediated by Tech's activation of RhoA as they are not mimicked by a mutant Tech construct lacking RhoA GEF activity and are blocked by C3 transferase, a selective inhibitor of RhoA. Furthermore, Tech-induced increases in SRF activity are suppressed by a dominant negative MAL construct. These findings demonstrate that RhoA signaling pathways are able to regulate transcription in neurons by triggering translocation of the SRF co-activator MAL.
Tabuchi
Akiko
A
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Estevez
Marcel
M
Henderson
Jennifer A
JA
Marx
Ruth
R
Shiota
Jun
J
Nakano
Hiroyasu
H
Baraban
Jay M
JM
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D007947:Leukemia, Megakaryoblastic, Acute / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D009474:Neurons / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators; D014162:Transfection; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; C431575:MRTFA protein, human; D015514:Oncogene Proteins, Fusion; C431574:RBM15 protein, human; D016601:RNA-Binding Proteins; D026362:Serum Response Factor; D015534:Trans-Activators; D020742:rhoA GTP-Binding Protein