Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
A secretagogin locus of the mammalian hypothalamus controls stress hormone release
Show others and affiliations
2015 (English)In: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 34, no 1, 36-54 p.Article in journal (Refereed) Published
Abstract [en]

A 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.

Place, publisher, year, edition, pages
2015. Vol. 34, no 1, 36-54 p.
Keyword [en]
acute stress, Ca2+ sensor, HPA axis, vesicular release
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:kth:diva-159352DOI: 10.15252/embj.201488977ISI: 000347167900004PubMedID: 25430741Scopus ID: 2-s2.0-84920440440OAI: oai:DiVA.org:kth-159352DiVA: diva2:785087
Funder
Swedish Research CouncilNovo NordiskThe Karolinska Institutet's Research FoundationWellcome trust, 094476/Z/10/ZScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20150202

Available from: 2015-02-02 Created: 2015-01-29 Last updated: 2017-12-05Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedScopus

Authority records BETA

Uhlén, Mathias

Search in DiVA

By author/editor
Uhlén, Mathias
By organisation
Proteomics and NanobiotechnologyScience for Life Laboratory, SciLifeLab
In the same journal
EMBO Journal
Biochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 42 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf