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Publication : Opposing functions of chondroitin sulfate and heparan sulfate during early neuronal polarization.

First Author  Nishimura K Year  2010
Journal  Neuroscience Volume  169
Issue  4 Pages  1535-47
PubMed ID  20600662 Mgi Jnum  J:165210
Mgi Id  MGI:4836447 Doi  10.1016/j.neuroscience.2010.06.027
Citation  Nishimura K, et al. (2010) Opposing functions of chondroitin sulfate and heparan sulfate during early neuronal polarization. Neuroscience 169(4):1535-47
abstractText  Axon-dendrite polarity of neurons is essential for information processing in the nervous system. Here we studied the functions of chondroitin sulfate (CS) and heparan sulfate (HS) in neuronal polarization using cultured dissociated hippocampal neurons. Immunohistochemical analyses of early cultured neurons indicated the distribution of these glycosaminoglycans to be quite different. While CS epitopes were accumulated in the focal contacts present in axons and cell bodies, those of HS were detected ubiquitously on the cell surface including on dendrites and axons. Treatment with chondroitinase (CHase) ABC, which degrades CS, and knockdown of a CS sulfotransferase, N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (4,6-ST), which is involved in the biosynthesis of oversulfated structures, induced the formation of multiple axons in hippocampal neurons. Time-lapse recordings revealed the multiple axons of CHase ABC-treated neurons to be highly unstable, extending and retracting, repeatedly. CHase ABC-treatments suggested that CS is involved in the formation of phosphorylated focal adhesion kinase-positive focal contacts. Thus, CS may enhance integrin signaling in the nascent axons, supporting axon specification. On the other hand, when neurons were treated with heparitinases that specifically degrade HS, neurons with a single axon increased. The axons of HSase-treated neurons extended steadily and showed almost no retraction. These results suggest that CS stabilizes and HS destabilizes the growth of axons in an opposing manner, contributing to early neuronal polarization.
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