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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 (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
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
  • 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
2018-04-29 04:37:36
@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},
  keyword      = {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          = {http://dx.doi.org/10.1016/j.yexcr.2017.03.021},
  volume       = {354},
  year         = {2017},
}