Nucleolin is a nuclear target of heparan sulfate derived from glypican-1
(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
- Cheng, Fang LU ; Belting, Mattias LU ; Fransson, Lars Åke LU and Mani, Katrin LU
- organization
- publishing date
- 2017-01-23
- 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
- 2025-01-07 10:53:00
@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}}, }