CREB-induced transcriptional activation depends on mGluR6 in rod bipolar cells.
To investigate the molecular mechanisms of stimuli-induced transcriptional activation in neuronal cells, we have investigated the light-induced gene expression in the neural retina of rats. The immunoreactivity for phosphorylated cAMP responsive element binding protein (PCREB-IR) was expressed in the outer half of the inner nuclear layer (INL) and the ganglion cell layer (GCL) after 5 min exposure to steady light also in mice. In addition to these cells, PCREB-IR was also detected in the inner border of the INL after 5 min exposure to flashing light. Both steady and flashing lights induced c-fos mRNA in the same types of cells as the PCREB-IR-positive cells. Majority of PCREB immunoreactive nuclei in the outer half of the INL were also immunopositive for anti-protein kinase C alpha (PKC alpha), a marker of rod bipolar cells, while CaM kinase IV immunoreactivity was not detected in these cells. PCREB-IR and c-fos gene expression in the PKC alpha positive rod bipolar cells were lost in mice lacking metabotropic glutamate receptor 6 (mGluR6). Thus, we propose that the transcriptional response of CREB to light stimulation in rod bipolar cells is regulated via mGluR6.
Department of Ophthalmology, Hokkaido University School of Medicine, Sapporo, Japan. kyoshida@ucsd.edu
K
K
Yoshida
J
J
Imaki
Y
Y
Okamoto
H
H
Iwakabe
H
H
Fujisawa
A
A
Matsuda
S
S
Nakanisi
H
H
Matsuda
M
M
Hagiwara
D000818:Animals; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000378:metabolism*; D014158:Transcription, Genetic
D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D018094:Receptors, Metabotropic Glutamate; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517685:Camk4 protein, mouse