Journal
JOURNAL OF CELL SCIENCE
Volume 121, Issue 18, Pages 3083-3091Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.032649
Keywords
chondroitin sulfate proteoglycan; sulfation; axonal guidance; axonal growth
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Funding
- Intramural NIH HHS [Z99 HL999999] Funding Source: Medline
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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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