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dc.contributor.authorRomanov, Roman A.
dc.contributor.authorAlpár, Alán
dc.contributor.authorZhang, Ming-Dong
dc.contributor.authorZeisel, Amit
dc.contributor.authorCalas, André
dc.contributor.authorLandry, Marc
dc.contributor.authorFuszard, Matthew Alexander
dc.contributor.authorShirran, Sally Lorna
dc.contributor.authorSchnell, Robert
dc.contributor.authorDobolyi, Árpád
dc.contributor.authorOláh, Márk
dc.contributor.authorSpence, Lauren
dc.contributor.authorMulder, Jan
dc.contributor.authorMartens, Henrik
dc.contributor.authorPalkovits, Miklós
dc.contributor.authorUhlen, Mathias
dc.contributor.authorSitte, Harald H.
dc.contributor.authorBotting, Catherine Helen
dc.contributor.authorWagner, Ludwig
dc.contributor.authorLinnarsson, Sten
dc.contributor.authorHökfelt, Tomas
dc.contributor.authorHarkany, Tibor
dc.identifier.citationRomanov , R A , Alpár , A , Zhang , M-D , Zeisel , A , Calas , A , Landry , M , Fuszard , M A , Shirran , S L , Schnell , R , Dobolyi , Á , Oláh , M , Spence , L , Mulder , J , Martens , H , Palkovits , M , Uhlen , M , Sitte , H H , Botting , C H , Wagner , L , Linnarsson , S , Hökfelt , T & Harkany , T 2015 , ' A secretagogin locus of the mammalian hypothalamus controls stress hormone release ' , EMBO Journal , vol. 34 , no. 1 , pp. 36-54 .
dc.identifier.otherORCID: /0000-0003-3516-3507/work/32169111
dc.descriptionThis work was supported by the Swedish Research Council (T.Ha., T.Hö.), Hjärnfonden (T.Ha.), the Petrus and Augusta Hedlunds Foundation (T.Ha., T.Hö.), the Novo Nordisk Foundation (T.Ha., T.Hö.), Karolinska Institutet (T.Hö.), the Medical University of Vienna (T.Ha.), ANR (France, ANR-10-INBS-04-01, M.L.), the European Commission (PAINCAGE grant, T.Ha.) and the Wellcome Trust (094476/Z/10/Z, equipment grant, C.H.B. and postdoctoral research fellowship, M.F.).en
dc.description.abstractA hierarchical hormonal cascade along the hypothalamic-pituitary-adrenal axis orchestrates bodily responses to stress. Although corticotropin-releasing hormone (CRH), produced by parvocellular neurons of the hypothalamic paraventricular nucleus (PVN) and released into the portal circulation at the median eminence, is known to prime downstream hormone release, the molecular mechanism regulating phasic CRH release remains poorly understood. Here, we find a cohort of parvocellular cells interspersed with magnocellular PVN neurons expressing secretagogin. Single-cell transcriptome analysis combined with protein interactome profiling identifies secretagogin neurons as a distinct CRH-releasing neuron population reliant on secretagogin's Ca2+ sensor properties and protein interactions with the vesicular traffic and exocytosis release machineries to liberate this key hypothalamic releasing hormone. Pharmacological tools combined with RNA interference demonstrate that secretagogin's loss of function occludes adrenocorticotropic hormone release from the pituitary and lowers peripheral corticosterone levels in response to acute stress. Cumulatively, these data define a novel secretagogin neuronal locus and molecular axis underpinning stress responsiveness.
dc.relation.ispartofEMBO Journalen
dc.subjectAcute stressen
dc.subjectCa2+ sensoren
dc.subjectHPA axisen
dc.subjectVesicular releaseen
dc.subjectR Medicine (General)en
dc.subjectQM Human anatomyen
dc.subjectSDG 3 - Good Health and Well-beingen
dc.titleA secretagogin locus of the mammalian hypothalamus controls stress hormone releaseen
dc.typeJournal articleen
dc.contributor.sponsorThe Wellcome Trusten
dc.contributor.institutionUniversity of St Andrews. School of Chemistryen
dc.contributor.institutionUniversity of St Andrews. EaSTCHEMen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.description.statusPeer revieweden

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