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Glycobiology Advance Access originally published online on September 12, 2006
Glycobiology 2006 16(12):1251-1261; 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

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

Katrin Mani, Fang Cheng and Lars-Åke Fransson1

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

1 To whom correspondence should be addressed; e-mail: lars-ake.fransson{at}med.lu.se

Received on June 1, 2006; revised on August 21, 2006; accepted on September 5, 2006

The recycling heparan sulfate (HS)-containing proteoglycan glypican-1 (Gpc-1) is processed by nitric oxide (NO)-catalyzed deaminative cleavage of its HS chains at N-unsubstituted glucosamines. This generates anhydromannose (anMan)-containing HS 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 anMan-positive degradation products generated constitutively in human bladder carcinoma cell line (T24) or fibroblasts appeared neither in caveolin-1-associated vesicles nor in lysosomes. In Niemann–Pick C-1 (NPC-1) fibroblasts, where deaminative degradation is abrogated, formation of anMan-positive products can be restored by ascorbate. These products colocalized with Rab7, a marker for late endosomes. When NO-catalyzed degradation of HS was depressed in mouse neuroblastoma cell line (N2a) by using 3-ß[2(diethylamino) ethoxy]androst-5-en-17-one (U18666A), both ascorbate and dehydroascorbic acid restored formation of anMan-positive products that colocalized with Rab7. In T24 cells, constitutively generated anMan-positive products colocalized with both Rab7 and Rab9, whereas 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 HS. This could also be overcome by the addition of ascorbate, which induced formation of anMan-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 HS may begin in early endosomes but is mainly taking place in late endosomes.

Key words: cholesterol / endosomes / glypican / heparan sulfate / nitric oxide


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 J. Biol. Chem.Home page
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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