Chondroitin Sulfate/Dermatan Sulfate Hybrid Chains in the Development of Cerebellum

Mitsunaga, Chie; Mikami, Tadahisa; Mizumoto, Shuji; Fukuda, Junko; Sugahara, Kazuyuki

doi:10.1074/jbc.m510870200

Cited by 50 publications

(27 citation statements)

References 56 publications

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“…Studies on the dissaccharides of CSs and DSs in the brain indicated that blocks of IdoA, which are the principal structures of DS patterns, are dramatically increased during development of the cerebellum, accompanied by a downregulation of CS patterns (Mitsunaga et al, 2006). These observations suggest that DS chains play important roles in CNS development.…”

Section: Discussionmentioning

confidence: 75%

Dermatan sulfotransferase Chst14/D4st1, but not chondroitin sulfotransferase Chst11/C4st1, regulates proliferation and neurogenesis of neural progenitor cells

Bian

Akyüz

Bernreuther

et al. 2011

Journal of Cell Science

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SummaryChondroitin sulfates (CSs) and dermatan sulfates (DSs) are enriched in the microenvironment of neural stem cells (NSCs) during development and in the adult neurogenic niche, and have been implicated in mechanisms governing neural precursor migration, proliferation and differentiation. In contrast to previous studies, in which a chondroitinaseABC-dependent unselective deglycosylation of both CSs and DSs was performed, we used chondroitin 4-O-sulfotransferase-1 (Chst11/C4st1)-and dermatan 4-O-sulfotransferase-1 (Chst14/D4st1)-deficient NSCs specific for CSs and DSs, respectively, to investigate the involvement of specific sulfation profiles of CS and DS chains, and thus the potentially distinct roles of CSs and DSs in NSC biology. In comparison to wild-type controls, deficiency for Chst14 resulted in decreased neurogenesis and diminished proliferation of NSCs accompanied by increased expression of GLAST and decreased expression of Mash-1, and an upregulation of the expression of the receptors for fibroblast growth factor-2 (FGF-2) and epidermal growth factor (EGF). By contrast, deficiency in Chst11 did not influence NSC proliferation, migration or differentiation. These observations indicate for the first time that CSs and DSs play distinct roles in the self-renewal and differentiation of NSCs.

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Section: Discussionmentioning

confidence: 75%

Dermatan sulfotransferase Chst14/D4st1, but not chondroitin sulfotransferase Chst11/C4st1, regulates proliferation and neurogenesis of neural progenitor cells

Bian

Akyüz

Bernreuther

et al. 2011

Journal of Cell Science

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“…Thus, secondary storage of dermatan sulfate in Sanfilippo cells is consistent with the idea that the combination of heparan sulfate and dermatan sulfate storage might contribute to pathology. Notably, although secondary accumulation of dermatan sulfate was shown to cause only a modest increase in overall glycosaminoglycan levels in Sanfilippo fibroblasts (ϳ10 -20%), the contribution of secondary dermatan sulfate to total storage levels may be much greater in tissues that produce high amounts of this glycosaminoglycan such as the brain (34,35). Future analysis of secondary dermatan sulfate storage in other cell types, particularly in the brain, will be necessary to substantiate the biological significance of our findings.…”

Section: Discussionmentioning

confidence: 98%

Secondary Storage of Dermatan Sulfate in Sanfilippo Disease

Lamanna

Lawrence

Sarrazin

et al. 2011

Journal of Biological Chemistry

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Mucopolysaccharidoses are a group of genetically inherited disorders that result from the defective activity of lysosomal enzymes involved in glycosaminoglycan catabolism, causing their intralysosomal accumulation. Sanfilippo disease describes a subset of mucopolysaccharidoses resulting from defects in heparan sulfate catabolism. Sanfilippo disorders cause severe neuropathology in affected children. The reason for such extensive central nervous system dysfunction is unresolved, but it may be associated with the secondary accumulation of metabolites such as gangliosides. In this article, we describe the accumulation of dermatan sulfate as a novel secondary metabolite in Sanfilippo. Based on chondroitinase ABC digestion, chondroitin/dermatan sulfate levels in fibroblasts from Sanfilippo patients were elevated 2-5-fold above wild-type dermal fibroblasts. Lysosomal turnover of chondroitin/dermatan sulfate in these cell lines was significantly impaired but could be normalized by reducing heparan sulfate storage using enzyme replacement therapy. Examination of chondroitin/dermatan sulfate catabolic enzymes showed that heparan sulfate and heparin can inhibit iduronate 2-sulfatase. Analysis of the chondroitin/dermatan sulfate fraction by chondroitinase ACII digestion showed dermatan sulfate storage, consistent with inhibition of iduronate 2-sulfatase. The discovery of a novel storage metabolite in Sanfilippo patients may have important implications for diagnosis and understanding disease pathology.

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“…1A). Although most of the disaccharide units are monosulfated ones that are called the A unit (GlcA␤1-3GalNAc(4-O-sulfate)) and C unit (GlcA␤1-3GalNAc(6-O-sulfate)), a minor but significant portion is disulfated (2,21,22). Recent studies revealed that the disulfated disaccharide units, which are classified into iB (IdoA(2-O-sulfate)␣1-3GalNAc(4-O-sulfate)), D (GlcA(2-Osulfate)␤1-3GalNAc(6-O-sulfate)), and E (GlcA␤1-3Gal-NAc(4,6-O-disulfate)) units (Fig.…”

mentioning

confidence: 99%

Oversulfated Chondroitin Sulfate Plays Critical Roles in the Neuronal Migration in the Cerebral Cortex

Ishii

Maeda

2008

Journal of Biological Chemistry

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Chondroitin Sulfate/Dermatan Sulfate Hybrid Chains in the Development of Cerebellum

Cited by 50 publications

References 56 publications

Dermatan sulfotransferase Chst14/D4st1, but not chondroitin sulfotransferase Chst11/C4st1, regulates proliferation and neurogenesis of neural progenitor cells

Dermatan sulfotransferase Chst14/D4st1, but not chondroitin sulfotransferase Chst11/C4st1, regulates proliferation and neurogenesis of neural progenitor cells

Secondary Storage of Dermatan Sulfate in Sanfilippo Disease

Oversulfated Chondroitin Sulfate Plays Critical Roles in the Neuronal Migration in the Cerebral Cortex

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