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Opioid precursor protein isoform is targeted to the cell nuclei in the human brain.
Kononenko, Olga; Bazov, Igor; Watanabe, Hiroyuki; Gerashchenko, Ganna; Dyachok, Oleg; Verbeek, Dineke S; Alkass, Kanar; Druid, Henrik; Andersson, Malin; Mulder, Jan; Svenningsen, Åsa Fex; Rajkowska, Grazyna; Stockmeier, Craig A; Krishtal, Oleg; Yakovleva, Tatiana; Bakalkin, Georgy.
Afiliación
  • Kononenko O; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala 751 24, Sweden; State Key Lab for Molecular Biology, Bogomoletz Institute of Physiology, Kiev 01024, Ukraine.
  • Bazov I; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala 751 24, Sweden. Electronic address: Igor.Bazov@farmbio.uu.se.
  • Watanabe H; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala 751 24, Sweden.
  • Gerashchenko G; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala 751 24, Sweden; Department of Functional Genomics, Institute Molecular Biology, Kiev 03680, Ukraine.
  • Dyachok O; Department of Medical Cell Biology, Uppsala University, 751 23, Sweden.
  • Verbeek DS; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen 30001, Netherlands.
  • Alkass K; Department of Forensic Medicine, Karolinska Institute, Stockholm 171 77, Sweden.
  • Druid H; Department of Forensic Medicine, Karolinska Institute, Stockholm 171 77, Sweden.
  • Andersson M; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala 751 24, Sweden.
  • Mulder J; Department of Neuroscience, Science for Life Laboratory, Karolinska Institute, Stockholm 171 77, Sweden.
  • Svenningsen ÅF; Institute of Molecular Medicine-Neurobiology Research, University of Southern Denmark, Odense 5000, Denmark.
  • Rajkowska G; Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson 2500, USA.
  • Stockmeier CA; Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson 2500, USA.
  • Krishtal O; State Key Lab for Molecular Biology, Bogomoletz Institute of Physiology, Kiev 01024, Ukraine.
  • Yakovleva T; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala 751 24, Sweden.
  • Bakalkin G; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala 751 24, Sweden.
Biochim Biophys Acta Gen Subj ; 1861(2): 246-255, 2017 Feb.
Article en En | MEDLINE | ID: mdl-27838394
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Núcleo Caudado / Núcleo Celular / Péptidos Opioides / Isoformas de Proteínas Límite: Adult / Aged / Aged80 / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Biochim Biophys Acta Gen Subj Año: 2017 Tipo del documento: Article País de afiliación: Ucrania Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Núcleo Caudado / Núcleo Celular / Péptidos Opioides / Isoformas de Proteínas Límite: Adult / Aged / Aged80 / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Biochim Biophys Acta Gen Subj Año: 2017 Tipo del documento: Article País de afiliación: Ucrania Pais de publicación: Países Bajos