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Glycobiology Advance Access published online on September 12, 2006
Glycobiology, doi:10.1093/glycob/cwl045
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received June 1, 2006
Revised August 21, 2006
Accepted September 5, 2006

Article

Constitutive and vitamin C-induced, NO-catalyzed release of heparan sulfate from recycling glypican-1 in late endosomes

Katrin Mani 1, Fang Cheng 1, and Lars-Åke Fransson 1 *

1 Department of Experimental Medical Science, Section of Neuroscience, Glycobiology Group, Lund University, Biomedical Centre A13, SE-221 84, Lund, Sweden

* To whom correspondence should be addressed.
Lars-Åke Fransson, E-mail: lars-ake.fransson{at}med.lu.se


  Abstract

The recycling heparan sulfate-containing proteoglycan glypican-1 is processed by NO-catalyzed deaminative cleavage of its heparan sulfate chains at N-unsubstituted glucosamines. This generates anhydromannose-containing heparan sulfate degradation products that can be detected by a specific antibody. Here we have attempted to identify the intracellular compartments where these products are formed. The anhydromannose-positive degradation products generated constitutively in T24 carcinoma cells or fibroblasts appeared neither in caveolin-1 associated vesicles nor in lysosomes. In Niemann-Pick C1 fibroblasts, where deaminative degradation is abrogated, formation of anhydromannose-positive products can be restored by ascorbate. These products colocalized with Rab7, a marker for late endosomes. When NO-catalyzed degradation of heparan sulfate was depressed in N2a neuroblastoma cells by using (3-{beta}[2(diethylamino) ethoxy]androst-5-en-17-one), both ascorbate and dehydroascorbic acid restored formation of anhydromannose-positive products that colocalized with Rab7. In T24 cells, constitutively generated anhydromannose-positive products colocalized with both Rab7 and Rab9, while Gpc-1 colocalized with Rab9, a marker for transporting endosomes. Inhibition of endosomal acidification, which blocks transfer from early (Rab5) to late (Rab7) endosomes, abrogated deaminative degradation of heparan sulfate. This could also be overcome by addition of ascorbate, which induced formation of anhydromannose-positive degradation products that colocalized with Rab7. After 35S-sulfate labeling, similar degradation products were recovered in Rab7-positive vesicles. We conclude that NO-catalyzed degradation of heparan sulfate may begin in early endosomes but is mainly taking place in late endosomes.

Keywords: Cholesterol/Endosomes/Glypican/Heparan sulfate/Nitric oxide.
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K. Mani, F. Cheng, and L.-A. Fransson
Heparan Sulfate Degradation Products Can Associate with Oxidized Proteins and Proteasomes
J. Biol. Chem., July 27, 2007; 282(30): 21934 - 21944.
[Abstract] [Full Text] [PDF]


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