Publication: A novel pineal-specific product of the oligopeptide transporter PepT1 gene: Circadian expression mediated by cAMP activation of an intronic promoter
Issued Date
2005-04-29
Resource Type
ISSN
00219258
Other identifier(s)
2-s2.0-20444467669
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Biological Chemistry. Vol.280, No.17 (2005), 16851-16860
Suggested Citation
Pascaline Gaildrat, Morten Møller, Sujira Mukda, Ann Humphries, David A. Carter, Vadivel Ganapathy, David C. Klein A novel pineal-specific product of the oligopeptide transporter PepT1 gene: Circadian expression mediated by cAMP activation of an intronic promoter. Journal of Biological Chemistry. Vol.280, No.17 (2005), 16851-16860. doi:10.1074/jbc.M414587200 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/16356
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Title
A novel pineal-specific product of the oligopeptide transporter PepT1 gene: Circadian expression mediated by cAMP activation of an intronic promoter
Abstract
The oligopeptide transporter 1, PepT1, is a member of the Slc15 family of 12 membrane-spanning domain transporters; PepT1 has proton/peptide cotransport activity and is selectively expressed in intestinal epithelial cells, where it is responsible for the nutritional absorption of di- and tri-peptides. Here, a novel PepT1 gene product has been identified in the rat pineal gland, termed pgPepT1. It encodes a 150-amino acid protein encompassing the C-terminal 3 membrane-spanning domains of intestinal PepT1 protein, with 3 additional N-terminal residues. Expression of pgPepT1 appears to be restricted to the pineal gland and follows a marked circadian pattern with >100-fold higher levels of mRNA occurring at night; this is accompanied by an accumulation of membrane-associated pgPepT1 protein (∼16 kDa). The daily rhythm in pgPepT1 mRNA is regulated by the well described neural pathway that controls pineal melatonin production. This includes the retina, the circadian clock in the suprachiasmatic nucleus, central structures, and projections from the superior cervical ganglia; activation of this pathway results in the release of norepinephrine. Here it was found that pgPepT1 expression is mediated by a norepinephrine → cyclic AMP mechanism that activates an alternative promoter located in intron 20 of the gene. pgPepT1 protein was found to have transporter-modulator activity; it could contribute to circadian changes in pineal function through this mechanism.