Role du calcium dans les processus de couplage stimulus-secretion dans la cellule corticosurrenalienne chez les amphibiens

SIGLECNRS T 59332 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Urotensine II et somatostatine : les retrouvailles de deux vieilles cousines

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New insight into the molecular evolution of the somatostatin family

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Cloning, sequence analysis and tissue distribution of the mouse and rat urotensin II precursors11The sequences reported in this paper have been deposited in the GenBank database [accession numbers AF172175 (mouse prepro-UII) and AF172174 (rat prepro-UII)].

AbstractUrotensin II (UII) is a cyclic neuropeptide initially isolated from the caudal neurosecretory system of teleost fish. The recent cloning of the UII precursor in frog and human has demonstrated that the peptide is not restricted to the fish urophysis but that it is also expressed in the central nervous system of tetrapods. Here, we describe the characterization of the cDNAs encoding prepro-UII in mouse and rat. A comparison of the primary structures of mouse and rat UII with those of other vertebrate UII reveals that the sequence of the cyclic region of the molecule (CFWKYC) has been fully conserved. In contrast, the N-terminal flanking domain of prepro-UII has markedly diverged with only 48% sequence identity between the mouse or rat and the human precursors. In situ hybridization histochemistry showed that the prepro-UII gene is predominantly expressed in motoneurons of the brainstem and spinal cord, suggesting that UII may play a role in the control of neuromuscular functions

Selenoprotein T is a key player in ER proteostasis, endocrine homeostasis and neuroprotection

International audienceSelenoprotein T (SELENOT, SELT) is a thioredoxin-like enzyme anchored at the endoplasmic reticulum (ER) membrane, whose primary structure is highly conserved during evolution. SELENOT is abundant in embryonic tissues and its activity is essential during development since its gene knockout in mice is lethal early during embryogenesis. Although its expression is repressed in most adult tissues, SELENOT remains particularly abundant in endocrine organs such as the pituitary, pancreas, thyroid and testis, suggesting an important role of this selenoprotein in hormone production. Our recent studies showed indeed that SELENOT plays a key function in insulin and corticotropin biosynthesis and release by regulating ER proteostasis. Although SELENOT expression is low or undetectable in most cerebral structures, its gene conditional knockout in brain provokes anatomical alterations that impact mice behavior. This suggests that SELENOT also plays an important role in brain development and function. In addition, SELENOT is induced after injury in brain or liver and exerts a cytoprotective effect. Thus, the data gathered during the last ten years of intense investigation of this newly discovered thioredoxin-like enzyme point to an essential function during development and in adult endocrine organs or lesioned brain, most likely by regulating ER redox circuits that control homeostasis and survival of cells with intense metabolic activity

Impact of gene/genome duplications on the evolution of the urotensin II and somatostatin families

International audienceThe present review describes the molecular evolution of two phylogenetically related families of neuropeptides, the urotensin II (UII) and somatatostatin (SS) families. The UII family consists of four paralogous genes called UII, URP, URP1 and URP2 and the SS family is composed of six paralogous genes named SS1, SS2, SS3, SS4, SS5 and SS6. All these paralogs are present in teleosts, while only four of them, UII, URP, SS1 and SS2 are detected in tetrapods. Comparative genomics showed that most of these genes, namely UII, URP, URP1 and URP2 on the one hand and SS1, SS2 and SS5 on the other hand arose through the 2R. In contrast, the teleost-specific 3R had a much more moderate impact since it only concerned the UII and SS1 genes, which once duplicated, generated a second UII copy and SS4, respectively. The two remaining genes, SS3 and SS6, arose through tandem duplications of the SS1 and SS2 genes respectively, probably in the stem lineage of actinopterygians, before the emergence of teleosts. The history of the UII and SS families has also been marked by massive gene lost, both in tetrapods and in teleosts, but only after the 3R in this latter lineage. Finally, ancestral UII and SS genes are thought to have arisen through tandem duplication of a single ancestral gene, largely before the 1R. An important challenge for the future will be to understand the physiological significance of the molecular diversity of these two families

Chromosomal localization of three somatostatin genes in zebrafish. Evidence that the [Pro2]-somatostatin-14 isoform and cortistatin are encoded by orthologous genes

International audienceThere is now evidence for the existence of two somatostatin genes in most vertebrate species, and even three somatostatin genes in teleosts. To help clarify the evolutionary relationships between the different somatostatin isoforms currently known, we characterized the somatostatin loci in a teleost species, the zebrafish Danio rerio, and compared them with the corresponding regions in the human and pufferfish genomes. The occurrence of three somatostatin genes, termed SS1, SS2 and SSII, has been previously demonstrated in the zebrafish. Radiation hybrid mapping assigned these three genes to linkage groups 15, 23 and 2, respectively. Conserved synteny of the zebrafish SS2 gene and the human cortistatin gene was revealed by comparative genomic analysis, indicating that mammalian cortistatin is orthologous to the SS2 variant of non-mammalian species. In contrast, using a similar approach, it was not possible to identify the evolutionary relationships between the atypical SSII gene of zebrafish and the other teleost SSII genes