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Nucleolin is a nuclear target of heparan sulfate derived from glypican-1

Cheng, Fang LU ; Belting, Mattias LU ; Fransson, Lars Åke LU and Mani, Katrin LU orcid (2017) In Experimental Cell Research 354(1). p.31-39
Abstract

The recycling, S-nitrosylated heparan sulfate (HS) proteoglycan glypican-1 releases anhydromannose (anMan)-containing HS chains by a nitrosothiol-catalyzed cleavage in endosomes that can be constitutive or induced by ascorbate. The HS-anMan chains are then transported to the nucleus. A specific nuclear target for HS-anMan has not been identified. We have monitored endosome-to-nucleus trafficking of HS-anMan by deconvolution and confocal immunofluorescence microscopy using an anMan-specific monoclonal antibody in non-growing, ascorbate-treated, and growing, untreated, wild-type mouse embryonic fibroblasts and hypoxia-exposed Alzheimer mouse Tg2576 fibroblasts and human U87 glioblastoma cells. In all cells, nuclear HS-anMan targeted a... (More)

The recycling, S-nitrosylated heparan sulfate (HS) proteoglycan glypican-1 releases anhydromannose (anMan)-containing HS chains by a nitrosothiol-catalyzed cleavage in endosomes that can be constitutive or induced by ascorbate. The HS-anMan chains are then transported to the nucleus. A specific nuclear target for HS-anMan has not been identified. We have monitored endosome-to-nucleus trafficking of HS-anMan by deconvolution and confocal immunofluorescence microscopy using an anMan-specific monoclonal antibody in non-growing, ascorbate-treated, and growing, untreated, wild-type mouse embryonic fibroblasts and hypoxia-exposed Alzheimer mouse Tg2576 fibroblasts and human U87 glioblastoma cells. In all cells, nuclear HS-anMan targeted a limited number of sites of variable size where it colocalized with DNA and nucleolin, an established marker for nucleoli. HS-anMan also colocalized with ethynyl uridine-tagged nascent RNA and two acetylated forms of histone H3. Acute hypoxia increased the formation of HS-anMan in both Tg2576 and U87 cells. A portion of HS-anMan colocalized with nucleolin at small discrete sites, while most of the nucleolin and nascent RNA was dispersed. In U87 cells, HS-anMan, nucleolin and nascent RNA reassembled after prolonged hypoxia. Nucleolar HS may modulate synthesis and/or release of rRNA.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Anhydromannose, Glypican, Heparan sulfate, Histones, Nucleolin, RNA
in
Experimental Cell Research
volume
354
issue
1
pages
31 - 39
publisher
Academic Press
external identifiers
  • scopus:85015829411
  • pmid:28300561
  • wos:000399867200004
ISSN
0014-4827
DOI
10.1016/j.yexcr.2017.03.021
language
English
LU publication?
yes
id
84554073-a49a-4c3e-b390-756ffa1609d4
date added to LUP
2017-04-06 08:37:50
date last changed
2024-02-29 12:27:00
@article{84554073-a49a-4c3e-b390-756ffa1609d4,
  abstract     = {{<p>The recycling, S-nitrosylated heparan sulfate (HS) proteoglycan glypican-1 releases anhydromannose (anMan)-containing HS chains by a nitrosothiol-catalyzed cleavage in endosomes that can be constitutive or induced by ascorbate. The HS-anMan chains are then transported to the nucleus. A specific nuclear target for HS-anMan has not been identified. We have monitored endosome-to-nucleus trafficking of HS-anMan by deconvolution and confocal immunofluorescence microscopy using an anMan-specific monoclonal antibody in non-growing, ascorbate-treated, and growing, untreated, wild-type mouse embryonic fibroblasts and hypoxia-exposed Alzheimer mouse Tg2576 fibroblasts and human U87 glioblastoma cells. In all cells, nuclear HS-anMan targeted a limited number of sites of variable size where it colocalized with DNA and nucleolin, an established marker for nucleoli. HS-anMan also colocalized with ethynyl uridine-tagged nascent RNA and two acetylated forms of histone H3. Acute hypoxia increased the formation of HS-anMan in both Tg2576 and U87 cells. A portion of HS-anMan colocalized with nucleolin at small discrete sites, while most of the nucleolin and nascent RNA was dispersed. In U87 cells, HS-anMan, nucleolin and nascent RNA reassembled after prolonged hypoxia. Nucleolar HS may modulate synthesis and/or release of rRNA.</p>}},
  author       = {{Cheng, Fang and Belting, Mattias and Fransson, Lars Åke and Mani, Katrin}},
  issn         = {{0014-4827}},
  keywords     = {{Anhydromannose; Glypican; Heparan sulfate; Histones; Nucleolin; RNA}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{1}},
  pages        = {{31--39}},
  publisher    = {{Academic Press}},
  series       = {{Experimental Cell Research}},
  title        = {{Nucleolin is a nuclear target of heparan sulfate derived from glypican-1}},
  url          = {{https://lup.lub.lu.se/search/files/31403733/23639639.pdf}},
  doi          = {{10.1016/j.yexcr.2017.03.021}},
  volume       = {{354}},
  year         = {{2017}},
}