期刊
JOURNAL OF CELL SCIENCE
卷 121, 期 18, 页码 3083-3091出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.032649
关键词
chondroitin sulfate proteoglycan; sulfation; axonal guidance; axonal growth
类别
资金
- Intramural NIH HHS [Z99 HL999999] Funding Source: Medline
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.
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