Chondroitin-4-sulfation negatively regulates axonal guidance and growth

被引：196

作者：

Wang, Hang ^{[1
]}

Katagiri, Yasuhiro ^{[1
]}

McCann, Thomas E. ^{[1
]}

Unsworth, Edward ^{[3
]}

Goldsmith, Paul ^{[3
]}

Yu, Zu-Xi ^{[2
]}

Tan, Fei ^{[1
]}

Santiago, Lizzie ^{[1
]}

Mills, Edward M. ^{[4
]}

Wang, Yu ^{[5
]}

Symes, Aviva J. ^{[5
]}

Geller, Herbert M. ^{[1
]}

机构：

[1] NCI, Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA

[2] NCI, NHLBI, NIH, Bethesda, MD 20892 USA

[3] NCI, Basic Res Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[4] Univ Texas Austin, Coll Pharm, Div Pharmacol Toxicol, Austin, TX 78712 USA

[5] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA

来源：

JOURNAL OF CELL SCIENCE | 2008年 / 121卷 / 18期

关键词：

chondroitin sulfate proteoglycan; sulfation; axonal guidance; axonal growth;

D O I：

10.1242/jcs.032649

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Glycosaminoglycan (GAG) side chains endow extracellular matrix proteoglycans with diversity and complexity based upon the length, composition and charge distribution of the polysaccharide chain. Using cultured primary neurons, we show that specific sulfation in the GAG chains of chondroitin sulfate mediates neuronal guidance cues and axonal growth inhibition. Chondroitin-4-sulfate (CS-A), but not chondroitin-6-sulfate (CS-C), exhibits a strong negative guidance cue to mouse cerebellar granule neurons. Enzymatic and gene-based manipulations of 4-sulfation in the GAG side chains alter their ability to direct growing axons. Furthermore, 4-sulfated chondroitin sulfate GAG chains are rapidly and significantly increased in regions that do not support axonal regeneration proximal to spinal cord lesions in mice. Thus, our findings show that specific sulfation along the carbohydrate backbone carries instructions to regulate neuronal function.

引用

页码：3083 / 3091

页数：9

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