Dominant negative ATF1 blocks cyclic AMP-induced neurite outgrowth in PC12D cells.
Extension of the neuronal process is a crucial step for establishment of the neuronal network. As CREB preferentially forms heterodimers with ATF1 in PC12D cells, we examined the roles of the CREB/ATF1 heterodimer on cyclic AMP (cAMP)-induced neurite extension, using originally constructed ATF1RL, which has a point mutation at the DNA binding domain of ATF1. Transient expression of ATF1RL suppressed the protein kinase A/CREB-induced expression of the CRE reporter gene as expected. Treatment with forskolin elicited a relatively poor mRNA induction for immediate early genes in PC12D-ATF1 RL cells, a PC12D cell line stably expressing ATF1RL, in comparison with the parental PC12D cells. Furthermore, the PC12D-ATF1RL cells were proved to be defective at cAMP-induced neurite outgrowth. In contrast, both the gene expression and the differentiation after nerve growth factor treatment noted in PC12D-ATF1RL cells were at the same levels as those in the parental cells. These data provide us the first evidence that links CREB/ATF1 to the cAMP-induced differentiation of PC12 cells.
Shimomura
A
A
Department of Anatomy, Nagoya University School of Medicine, Japan.
Okamoto
Y
Y
Hirata
Y
Y
Kobayashi
M
M
Kawakami
K
K
Kiuchi
K
K
Wakabayashi
T
T
Hagiwara
M
M
D051697:Activating Transcription Factor 1; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D000242:Cyclic AMP / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics; D004268:DNA-Binding Proteins; D019281:Dimerization; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D017781:Genes, Immediate-Early / Q000235:genetics; D016296:Mutagenesis / Q000502:physiology; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000648:ultrastructure; D016716:PC12 Cells; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D014162:Transfection
D051697:Activating Transcription Factor 1; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D000242:Cyclic AMP