TY - JOUR
T1 - Nuclear translocation of the SRF co-activator MAL in cortical neurons
T2 - Role of RhoA signalling
AU - Tabuchi, Akiko
AU - Estevez, Marcel
AU - Henderson, Jennifer A.
AU - Marx, Ruth
AU - Shiota, Jun
AU - Nakano, Hiroyasu
AU - Baraban, Jay M.
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
KW - Megakaryocytic acute leukemia
KW - Nuclear translocation
KW - Primary cortical cultures
KW - Rho GTPases
KW - Tech
KW - mDia
UR - http://www.scopus.com/inward/record.url?scp=21344453746&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=21344453746&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2005.03179.x
DO - 10.1111/j.1471-4159.2005.03179.x
M3 - Article
C2 - 15953360
AN - SCOPUS:21344453746
SN - 0022-3042
VL - 94
SP - 169
EP - 180
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 1
ER -