title: Selenoprotein T is a PACAP-regulated gene involved in intracellular Ca2+ mobilization and neuroendocrine secretion.
abstract: Selenoproteins contain the essential trace element selenium, the deficiency of which is associated with cancer or accelerated aging. Although selenoproteins are thought to be instrumental for the effects of selenium, the biological function of many of these proteins remains unknown. Here, we studied the role of selenoprotein T (SelT), a selenocysteine (Sec) -containing protein with no known function, which we have identified as a novel target gene of the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) during PC12 cell differentiation. SelT was found to be ubiquitously expressed throughout embryonic development and in adulthood in rat. Immunocytochemical analysis revealed that SelT is mainly localized to the endoplasmic reticulum through a hydrophobic domain. PACAP and cAMP induced a rapid and long-lasting increase in SelT gene expression in PC12 cells, in a Ca(2+)-dependent manner. These results suggested a possible role of SelT in PACAP signaling during PC12 cell differentiation. Indeed, overexpression of SelT in PC12 cells provoked an increase in the concentration of intracellular Ca(2+) ([Ca(2+)](i)) that was dependent on the Sec residue. Conversely, SelT gene knockdown inhibited the PACAP-induced increase in [Ca(2+)](i) and reduced hormone secretion. These findings demonstrate the implication of a selenoprotein in the regulation of Ca(2+) homeostasis and neuroendocrine secretion in response to a cAMP-stimulating trophic factor.
authors.affiliation: European Institute for Peptide Research (IFRMP 23), Laboratory of Cellular and Molecular Neuroendocrinology, INSERM U413, UA CNRS, University of Rouen 76821 Mont-St.-Aignan, France.
authors.forename: Luca
authors.initials: L
authors.lastname: Grumolato
authors.forename: Hafida
authors.initials: H
authors.lastname: Ghzili
authors.forename: Maité
authors.initials: M
authors.lastname: Montero-Hadjadje
authors.forename: Stéphane
authors.initials: S
authors.lastname: Gasman
authors.forename: Jean
authors.initials: J
authors.lastname: Lesage
authors.forename: Yannick
authors.initials: Y
authors.lastname: Tanguy
authors.forename: Ludovic
authors.initials: L
authors.lastname: Galas
authors.forename: Djida
authors.initials: D
authors.lastname: Ait-Ali
authors.forename: Jérôme
authors.initials: J
authors.lastname: Leprince
authors.forename: Nathalie C
authors.initials: NC
authors.lastname: Guérineau
authors.forename: Abdel G
authors.initials: AG
authors.lastname: Elkahloun
authors.forename: Alain
authors.initials: A
authors.lastname: Fournier
authors.forename: Didier
authors.initials: D
authors.lastname: Vieau
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
authors.forename: Youssef
authors.initials: Y
authors.lastname: Anouar
mesh_terms: D000818:Animals; D002118:Calcium / Q000032:analysis; D020013:Calcium Signaling; D002454:Cell Differentiation; D000242:Cyclic AMP; D004721:Endoplasmic Reticulum / Q000737:chemistry; D005786:Gene Expression Regulation; D009489:Neurosecretion; D016716:PC12 Cells; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000502:physiology*; D051381:Rats; D017279:Selenocysteine; D051140:Selenoproteins / Q000502:physiology*
chemical_list: D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; C495235:SELENOT protein, human; D051140:Selenoproteins; D017279:Selenocysteine; D000242:Cyclic AMP; D002118:Calcium