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First published online September 3, 2008

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CSPGs show axons the way

During neural development and regeneration, chondroitin sulfate – the glycosaminoglycan (GAG) component of chondroitin sulfate proteoglycans (CSPGs) – has been proposed to guide axonal growth by acting as a chemorepellent. Chondroitin can be sulfated at several sites on its carbohydrate backbone – but can the pattern of CSPG sulfation affect its axon-guiding activity? On page 3083, Herbert Geller and colleagues suggest that it can. The authors show that chondroitin-4-sulfate, but not chondroitin-6-sulfate, repels the growing axons of mouse cerebellar granule neurons; this effect is abolished when chondroitin-4-sulfate is treated with chondro-4-sulfatase. Moreover, reactive astrocytes (which inhibit axonal growth) upregulate CSPG expression and produce more 4-sulfated than 6-sulfated GAG chains. Knocking down endogenous chondroitin-4-O-sulfotransferase 1 (C4ST1) in these astrocytes depletes 4-sulfation and reduces the repellent activity of the conditioned medium; conversely, astrocytes in which C4ST1 is overexpressed have more 4-sulfated GAG chains and are much less permissive to neuronal growth. Importantly, the expression of 4-sulfated GAG chains by reactive astrocytes is acutely increased in a mouse model of spinal injury. Thus, the site of chondroitin sulfation affects its role in axon guidance.

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Chondroitin-4-sulfation negatively regulates axonal guidance and growth

Hang Wang, Yasuhiro Katagiri, Thomas E. McCann, Edward Unsworth, Paul Goldsmith, Zu-Xi Yu, Fei Tan, Lizzie Santiago, Edward M. Mills, Yu Wang, Aviva J. Symes, and Herbert M. Geller
JCS 2008 121: 3083-3091. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?