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

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

Kononenko, Olga (author): Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden

Bazov, Igor (author): Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden

Watanabe, Hiroyuki (author): Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden

Gerashchenko, Ganna (author): Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden; Institute Molecular Biology, Kiev, Ukraine

Dyachok, Oleg (author): Uppsala universitet,Institutionen för medicinsk cellbiologi,Uppsala University, Uppsala, Sweden

Verbeek, Dineke S (author): University of Groningen, Groningen, Netherlands

Alkass, Kanar (author): Karolinska Institutet

Druid, Henrik (author): Karolinska Institutet

Andersson, Malin (author): Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden

Mulder, Jan (author): Karolinska Institutet

Svenningsen, Åsa Fex (author): University of Southern Denmark, Odense, Denmark

Rajkowska, Grazyna (author): University of Mississippi Medical Center, Jackson, USA

Stockmeier, Craig A (author): University of Mississippi Medical Center, Jackson, USA

Krishtal, Oleg (author): Bogomoletz Institute of Physiology, Kiev, Ukraine

Yakovleva, Tatiana (author): Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden

Bakalkin, Georgy (author): Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Uppsala University, Uppsala, Sweden

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Elsevier BV, 2017
2017
English.
In: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002 .- 1878-2434 .- 0304-4165 .- 1872-8006. ; 1861:2, s. 246-255

Related links:: https://europepmc.or...; show more...; https://doi.org/10.1...; https://urn.kb.se/re...; https://doi.org/10.1...; https://urn.kb.se/re...; http://kipublication...; show less...

Journal article (peer-reviewed)

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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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By the author/editor: Kononenko, Olga; Bazov, Igor; Watanabe, Hiroyu ...; Gerashchenko, Ga ...; Dyachok, Oleg; Verbeek, Dineke ...; show more...; Alkass, Kanar; Druid, Henrik; Andersson, Malin; Mulder, Jan; Svenningsen, Åsa ...; Rajkowska, Grazy ...; Stockmeier, Crai ...; Krishtal, Oleg; Yakovleva, Tatia ...; Bakalkin, Georgy; show less...

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NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

Articles in the publication: Biochimica et Bi ...

By the university: Uppsala University; Örebro University; Karolinska Institutet

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

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