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This Article Full Text Full Text (PDF) All Versions of this Article: fj.06-075820v1 22/6/1756    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Grumolato, L. Articles by Anouar, Y. PubMed PubMed Citation Articles by Grumolato, L. Articles by Anouar, Y.

Selenoprotein T is a PACAP-regulated gene involved in intracellular Ca²⁺ mobilization and neuroendocrine secretion

Luca Grumolato^*,1, Hafida Ghzili^*,1, Maité Montero-Hadjadje^*, Stéphane Gasman, Jean Lesage, Yannick Tanguy^*, Ludovic Galas^*, Djida Ait-Ali^*, Jérôme Leprince^*, Nathalie C. Guérineau, Abdel G. Elkahloun^||, Alain Fournier^¶, Didier Vieau, Hubert Vaudry^* and Youssef Anouar^*,2

^* INSERM U413, European Institute for Peptide Research (IFRMP 23), Laboratory of Cellular and Molecular Neuroendocrinology, UA CNRS, University of Rouen, Mont-Saint-Aignan, France;

Department of Neurotransmission and Neuroendocrine Secretion, UMR 7168/LC2 CNRS, Institut des Neurosciences Cellulaires et Intégratives, Université Louis Pasteur, Strasbourg, France;

Department of Adaptative Neurosciences and Physiology, Perinatal Stress Unit, University of Lille I, France;

CNRS UMR5203, INSERM U661, Functional Genomics Institute, Department of Endocrinology, University of Montpellier I et II, Montpellier, France;

^|| Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA; and

^¶ Institut National de la Recherche Scientifique-Institut Armand-Frappier, University of Quebec, Pointe Claire, Montréal, Canada

²Correspondence: 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. E-mail: youssef.anouar{at}univ-rouen.fr

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 Ca²⁺-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 Ca²⁺ ([Ca²⁺]_i) that was dependent on the Sec residue. Conversely, SelT gene knockdown inhibited the PACAP-induced increase in [Ca²⁺]_i and reduced hormone secretion. These findings demonstrate the implication of a selenoprotein in the regulation of Ca²⁺ homeostasis and neuroendocrine secretion in response to a cAMP-stimulating trophic factor.—Grumolato, L., Ghzili, H., Montero-Hadjadje, M., Gasman, S., Lesage, J., Tanguy, Y., Galas, L., Ait-Ali, D., Leprince, J., Guérineau, N. C., Elkahloun, A. G., Fournier, A., Vieau, D., Vaudry, H., Anouar, Y. Selenoprotein T is a PACAP-regulated gene involved in intracellular Ca²⁺ mobilization and neuroendocrine secretion.

Key Words: cell differentiation • pituitary adenylate cyclase-activating polypeptide • cAMP • PC12 cells