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 ...
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Elsevier BV,2017
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-316836
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-316836URI
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https://doi.org/10.1016/j.bbagen.2016.11.002DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-82996URI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:135082414URI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Shared first authorship for Kononenko O., Bazov I.
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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)
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Watanabe, HiroyukiUppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden(Swepub:uu)hirwa520
(author)
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Gerashchenko, GannaUppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden; Institute Molecular Biology, Kiev, Ukraine
(author)
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Dyachok, OlegUppsala universitet,Institutionen för medicinsk cellbiologi,Uppsala University, Uppsala, Sweden(Swepub:uu)olegdyac
(author)
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Verbeek, Dineke SUniversity of Groningen, Groningen, Netherlands
(author)
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Alkass, KanarKarolinska Institutet
(author)
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Druid, HenrikKarolinska Institutet
(author)
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Andersson, MalinUppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden(Swepub:uu)malan799
(author)
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Mulder, JanKarolinska Institutet
(author)
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Svenningsen, Åsa FexUniversity of Southern Denmark, Odense, Denmark
(author)
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Rajkowska, GrazynaUniversity of Mississippi Medical Center, Jackson, USA
(author)
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Stockmeier, Craig AUniversity of Mississippi Medical Center, Jackson, USA
(author)
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Krishtal, OlegBogomoletz Institute of Physiology, Kiev, Ukraine
(author)
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Yakovleva, TatianaUppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden(Swepub:uu)tatia678
(author)
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Bakalkin, GeorgyUppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden(Swepub:uu)gueba200
(author)
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Uppsala universitetInstitutionen för farmaceutisk biovetenskap
(creator_code:org_t)
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In:Biochimica et Biophysica Acta: Elsevier BV1861:2, s. 246-2550006-30021878-24340304-41651872-8006
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Kononenko, Olga
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Bazov, Igor
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Watanabe, Hiroyu ...
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Gerashchenko, Ga ...
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Verbeek, Dineke ...
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Alkass, Kanar
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Druid, Henrik
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Andersson, Malin
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Mulder, Jan
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Stockmeier, Crai ...
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Krishtal, Oleg
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