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

Ishii, Maki; Maeda, Nobuaki

doi:10.1074/jbc.m806331200

Cited by 74 publications

(72 citation statements)

References 48 publications

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“…Consistent with our findings is the impact of over-sulfated CS in in vivo neuronal migration (Ishii and Maeda, 2008) and loss of directional migration of aortic smooth muscle cells with reduced cell surface L-IdoUA content (Bartolini et al, 2013). This underlies the importance of DS and the downstream 2-O sulfation in mediating cell migration and adhesion (Malmström et al, 2012).…”

Section: Discussionsupporting

confidence: 89%

“…Over-sulfated CS is involved in neuronal migration and axon regeneration (Kwok et al, 2012, Maeda andNoda, 1998) and Ust knockdown lead to an altered neurite outgrowth (Ishii and Maeda, 2008). Furthermore, the lack of CS/DS 2-O sulfation in skin of decorin-deficient (Dcn 2/2 ) mice affects Fgf2 and Fgf7 binding and keratinocyte differentiation (Nikolovska et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Chondroitin/dermatan 2-O sulfotransferase potentiates Fgf2 induced cell migration

Nikolovska

Spillmann

Seidler

2014

Journal of Cell Science

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Fibroblast growth factor 2 (Fgf2) is involved in several biological functions. Fgf2 requires glycosaminoglycans, like chondroitin and dermatan sulfates (hereafter denoted CS/DS) as co-receptors. CS/ DS are linear polysaccharides composed of repeating disaccharide units and , which can be sulfated. Uronyl 2-O-sulfotransferase (Ust) introduces sulfation at the C2 of IdoUA and GlcUA resulting in over-sulfated units. Here, we investigated the role of Ust-mediated CS/DS 2-O sulfation in Fgf2-induced cell migration. We found that CHO-K1 cells overexpressing Ust contain significantly more CS/DS 2-O sulfated units, whereas Ust knockdown abolished CS/DS 2-O sulfation. These structural differences in CS/DS resulted in altered Fgf2 binding and increased phosphorylation of ERK1/2 (also known as MAPK3 and MAPK1, respectively). As a functional consequence of CS/DS 2-O sulfation and altered Fgf2 binding, cell migration and paxillin activation were increased. Inhibition of sulfation, knockdown of Ust and inhibition of FgfR resulted in reduced migration. Similarly, in 3T3 cells Fgf2 treatment increased migration, which was abolished by Ust knockdown. The proteoglycan controlling the CHO migration was syndecan 1. Knockdown of Sdc1 in CHO-K1 cells overexpressing Ust abolished cell migration. We conclude that the presence of distinctly sulfated CS/DS can tune the Fgf2 effect on cell migration.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Chondroitin/dermatan 2-O sulfotransferase potentiates Fgf2 induced cell migration

Nikolovska

Spillmann

Seidler

2014

Journal of Cell Science

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“…Various combinations of these units generate tremendous structural diversity, even in 1 CS chain, which carries information like "unit clustering" or "unit sequences." Recent reports indicate that cells may recognize specific unit sequences of CS, which has led to investigations into the molecular mechanism of CS recognition [7,[35][36][37][38][39][40][41]. …”

Section: Chondroitin Sulfate Proteoglycans In Neuronal Circuit Formationmentioning

confidence: 99%

“…Moreover, it can be used to prepare complexes of different types of CS chains on the same core protein. Since highly sulfated CS, for example D-or E-unit containing CS, is thought to be involved with neurite elongation or axonal guidance [7,28,29,36,39], it would be intriguing to use the complex with D-or E-unit containing CS in future investigations. The CS-biotin-streptavidin complex enables us to examine the relationship between the structural diversity of CS and its functional specificity.…”

Section: Biotinylated Chondroitin Sulfate and Artificial Chondroitin mentioning

confidence: 99%

Application of Chondroitin Sulfate Derivatives for Understanding Axonal Guidance in the Nervous System during Development

2013

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Neuronal axons and their growth cones recognize molecular guidance cues within the local environment, forming axonal pathways to produce precise neuronal networks during nervous system development. Chondroitin sulfates (CS), carbohydrate chains on chondroitin sulfate proteoglycans, exhibit great structural diversity and exert various influences on axons and growth cones as guidance cues or their modulators; however, the relationship between their structural diversity and function in axonal guidance is not well known. To uncover the roles of CS in axonal guidance, artificially modified hybrid molecules: CS derivatives of biotinylated CS and lipid-derivatized CS, were used. The experiments with biotinylated CS suggest that the growing axons act on their environment, modifying CS, and rendering it more favorable for their growth. The experiments with lipid-derivatized CS demonstrated that growth cones distinguish types of CS with different unit contents and are likely to discriminate the structural diversity of CS. The application of CS derivatives is useful in uncovering axon-environment interaction and structure-function relationship of CS directly.

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“…Chondroitin sulfate (CS)-PG constitutes the major population of GAGs in the central nervous system (CNS). CS-PG plays important roles in the developing and adult CNS with respect to the regulation of cell proliferation, differentiation, neuronal migration, neurite extension, neural plasticity, and axonal regeneration [2].…”

Section: Introductionmentioning

confidence: 99%

Paradoxical effects of chondroitin sulfate-E on Japanese encephalitis viral infection

Kim

Okumura

Sawa

et al. 2011

Biochemical and Biophysical Research Communications

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Glycosaminoglycans (GAGs) have diverse functions in the body and are involved in viral infection. The purpose of this study was to evaluate the possible roles of the E-disaccharide units GlcAβ1-3GalNAc(4,6-O-disulfate) of chondroitin sulfate (CS), a GAG involved in neuritogenesis and neuronal migration, in Japanese encephalitis virus (JEV) infection.Soluble CS-E (sCS-E) derived from squid cartilage inhibited JEV infection in African green monkey kidney-derived Vero cells and baby hamster kidney-derived BHK cells by interfering with viral attachment. In contrast, sCS-E enhanced viral infection in the mouse neuroblastoma cell line Neuro-2a, despite the fact that viral attachment to Neuro-2a cells was inhibited by sCS-E. This enhancement effect in Neuro-2a cells seemed to be related to increased viral RNA replication and was also observed in a rat infection model in which intracerebral coadministration of sCS-E with JEV in 17-day-old rats resulted in higher brain viral loads than in rats infected without sCS-E administration. These results show the paradoxical effects of sCS-E on JEV infection in different cell types and indicate that potential use of sCS-E as an antiviral agent against JEV infection should be approached with caution considering its effects in the neuron, the major target of JEV.

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

Cited by 74 publications

References 48 publications

Chondroitin/dermatan 2-O sulfotransferase potentiates Fgf2 induced cell migration

Chondroitin/dermatan 2-O sulfotransferase potentiates Fgf2 induced cell migration

Application of Chondroitin Sulfate Derivatives for Understanding Axonal Guidance in the Nervous System during Development

Paradoxical effects of chondroitin sulfate-E on Japanese encephalitis viral infection

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