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Search: id:"swepub:oai:DiVA.org:uu-316836" > Opioid precursor pr...

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  • Kononenko, OlgaUppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden (author)

Opioid precursor protein isoform is targeted to the cell nuclei in the human brain

  • Article/chapterEnglish2017

Publisher, publication year, extent ...

  • Elsevier BV,2017
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-316836
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-316836URI
  • https://doi.org/10.1016/j.bbagen.2016.11.002DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-82996URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:135082414URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Shared first authorship for Kononenko O., Bazov I.
  • BACKGROUND: Neuropeptide precursors are traditionally viewed as proteins giving rise to small neuropeptide molecules. Prodynorphin (PDYN) is the precursor protein to dynorphins, endogenous ligands for the κ-opioid receptor. Alternative mRNA splicing of neuropeptide genes may regulate cell- and tissue-specific neuropeptide expression and produce novel protein isoforms. We here searched for novel PDYN mRNA and their protein product in the human brain.METHODS: Novel PDYN transcripts were identified using nested PCR amplification of oligo(dT) selected full-length capped mRNA. Gene expression was analyzed by qRT-PCR, PDYN protein by western blotting and confocal imaging, dynorphin peptides by radioimmunoassay. Neuronal nuclei were isolated using fluorescence-activated nuclei sorting (FANS) from postmortem human striatal tissue. Immunofluorescence staining and confocal microscopy was performed for human caudate nucleus.RESULTS: Two novel human PDYN mRNA splicing variants were identified. Expression of one of them was confined to the striatum where its levels constituted up to 30% of total PDYN mRNA. This transcript may be translated into ∆SP-PDYN protein lacking 13 N-terminal amino acids, a fragment of signal peptide (SP). ∆SP-PDYN was not processed to mature dynorphins and surprisingly, was targeted to the cell nuclei in a model cellular system. The endogenous PDYN protein was identified in the cell nuclei in human striatum by western blotting of isolated neuronal nuclei, and by confocal imaging.CONCLUSIONS AND GENERAL SIGNIFICANCE: High levels of alternatively spliced ∆SP-PDYN mRNA and nuclear localization of PDYN protein suggests a nuclear function for this isoform of the opioid peptide precursor in human striatum.

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  • Bazov, IgorUppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden(Swepub:oru)ibv (author)
  • Watanabe, HiroyukiUppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden(Swepub:uu)hirwa520 (author)
  • Gerashchenko, GannaUppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden; Institute Molecular Biology, Kiev, Ukraine (author)
  • Dyachok, OlegUppsala universitet,Institutionen för medicinsk cellbiologi,Uppsala University, Uppsala, Sweden(Swepub:uu)olegdyac (author)
  • Verbeek, Dineke SUniversity of Groningen, Groningen, Netherlands (author)
  • Alkass, KanarKarolinska Institutet (author)
  • Druid, HenrikKarolinska Institutet (author)
  • Andersson, MalinUppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden(Swepub:uu)malan799 (author)
  • Mulder, JanKarolinska Institutet (author)
  • Svenningsen, Åsa FexUniversity of Southern Denmark, Odense, Denmark (author)
  • Rajkowska, GrazynaUniversity of Mississippi Medical Center, Jackson, USA (author)
  • Stockmeier, Craig AUniversity of Mississippi Medical Center, Jackson, USA (author)
  • Krishtal, OlegBogomoletz Institute of Physiology, Kiev, Ukraine (author)
  • Yakovleva, TatianaUppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden(Swepub:uu)tatia678 (author)
  • Bakalkin, GeorgyUppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden(Swepub:uu)gueba200 (author)
  • Uppsala universitetInstitutionen för farmaceutisk biovetenskap (creator_code:org_t)

Related titles

  • In:Biochimica et Biophysica Acta: Elsevier BV1861:2, s. 246-2550006-30021878-24340304-41651872-8006

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