RGD Reference Report - Cell-type specific induction of tryptophan hydroxylase-2 transcription by calcium mobilization. - Rat Genome Database

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Cell-type specific induction of tryptophan hydroxylase-2 transcription by calcium mobilization.

Authors: Lenicov, FR  Lemonde, S  Czesak, M  Mosher, TM  Albert, PR 
Citation: Lenicov FR, etal., J Neurochem. 2007 Dec;103(5):2047-57. Epub 2007 Sep 14.
RGD ID: 2317090
Pubmed: PMID:17868301   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1471-4159.2007.04903.x   (Journal Full-text)

Alterations in brain serotonin levels are implicated in major depression and are regulated by tryptophan hydroxylase-2 (TPH2). To study its regulation, we measured TPH2 RNA by quantitative RT-PCR in differentiated serotonergic rat raphe RN46A and GH4C1 pituitary cells, which express TPH2. Upon calcium mobilization using KCl (40 mmol/L), TPH2 RNA was rapidly (1 h) and strongly (> 10-fold) induced in differentiated RN46A cells, but not in GH4C1 cells. This effect was blocked by actinomycin D, implicating transcriptional activation. Similarly, calcium ionophore ionomycin induced TPH2 RNA by threefold in RN46A cells. To address the promoter sites involved, the transcription start site was identified and a series of TATA-containing TPH2 promoter-luciferase constructs were analyzed. In differentiated RN46A cells, the TPH2 promoter was induced 2.5-fold by ionomycin, similar to its action on TPH2 RNA. By contrast, ionomycin had no effect on TPH2 promoter activity in GH4C1 cells or TPH2-negative L6 myoblasts. Ionomycin sensitivity was localized to within 88 bp of the start site, containing putative CCATT-enhancer binding protein element, activator protein-1 and -2 (AP-1, AP-2) elements. These results are the first to identify calcium-mediated regulation of the proximal TPH2 promoter as critical for cell-specific TPH2 expression.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to calcium ion  IEP 2317090 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tph2  (tryptophan hydroxylase 2)


Additional Information