Gene structure of the human metabotropic glutamate receptor 5 and functional analysis of its multiple promoters in neuroblastoma and astroglioma cells

Corrado Corti, Richard W E Clarkson, Luca Crepaldi, Cinzia F. Sala, John H. Xuereb, Francesco Ferraguti

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The metabotropic glutamate receptor 5 (mGluR5) has a discrete tissue expression mainly limited to neural cells. Expression of mGluR5 is developmentally regulated and undergoes dramatic changes in association with neuropathological disorders. We report the complete genomic structure of the mGluR5 gene, which is composed of 11 exons and encompasses ∼563 kbp. Three clusters of multiple transcription initiation sites located on three distinct exons (IA, IB, and II), which undergo alternative splicing, have been identified. The 5′-flanking regions of these exons were isolated and, using a luciferase reporter gene assay, shown to possess active promoter elements in SKN-MC neuroblastoma and U178-MG astroglioma cells. Promoter IA was characterized by a CpG island; promoter IB contained a TATA box, and promoter II possessed three active Oct-1-binding sites. Preferential luciferase activity was observed in SKN-MC concomitant with differential DNA binding activity to several responsive elements, including CREB, Oct-1, C/EBP, and Brn-2. Exposure to growth factors produced enhanced expression of promoters IB and II in astroglioma cells and activation of NF-κB. These results suggest that alternative 5′-splicing and usage of multiple promoters may contribute regulatory mechanisms for tissue- and context-specific expression of the mGluR5 gene.

Original languageEnglish
Pages (from-to)33105-33119
Number of pages15
JournalJournal of Biological Chemistry
Volume278
Issue number35
DOIs
Publication statusPublished - Aug 29 2003

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Metabotropic Glutamate 5 Receptor
Functional analysis
Astrocytoma
Neuroblastoma
Genes
Exons
Alternative Splicing
Luciferases
Tissue
TATA Box
CpG Islands
5' Flanking Region
Transcription Initiation Site
Reporter Genes
Assays
Intercellular Signaling Peptides and Proteins
Chemical activation
Binding Sites
Association reactions
DNA

ASJC Scopus subject areas

  • Biochemistry

Cite this

Gene structure of the human metabotropic glutamate receptor 5 and functional analysis of its multiple promoters in neuroblastoma and astroglioma cells. / Corti, Corrado; Clarkson, Richard W E; Crepaldi, Luca; Sala, Cinzia F.; Xuereb, John H.; Ferraguti, Francesco.

In: Journal of Biological Chemistry, Vol. 278, No. 35, 29.08.2003, p. 33105-33119.

Research output: Contribution to journalArticle

Corti, Corrado ; Clarkson, Richard W E ; Crepaldi, Luca ; Sala, Cinzia F. ; Xuereb, John H. ; Ferraguti, Francesco. / Gene structure of the human metabotropic glutamate receptor 5 and functional analysis of its multiple promoters in neuroblastoma and astroglioma cells. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 35. pp. 33105-33119.
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