Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth.
Cell migration is central to development and post-traumatic regeneration. The differential increase in 6-sulphated chondroitins during axonal growth in both crushed sciatic nerves and brain development suggests that chondroitin 6-sulphotransferase-1 (C6ST-1) is a key enzyme that mediates cell migration in the process. We have cloned the cDNA of the C6ST-1 gene (C6st1) (GenBank accession number AF178689) from crushed sciatic nerves of adult rats and produced ribonucleotide probes accordingly to track signs of 6-sulphated chondroitins at the site of injury. We found C6st1 mRNA expression in Schwann cells emigrating from explants of both sciatic nerve segments and embryonic dorsal root ganglia. Immunocytochemistry indicated pericellular 6-sulphated chondroitin products around C6ST-1-expressing frontier cells. Motility analysis of frontier cells in cultures subjected to staged treatment with chondroitinase ABC indicated that freshly produced 6-sulphated chondroitin moieties facilitated Schwann cell motility, unlike restrictions resulting from proteoglycan interaction with matrix components. Sciatic nerve crush provided further evidence of in vivo upregulation of the C6ST-1 gene in mobile Schwann cells that guided axonal regrowth 1-14 days post crush; downregulation then accompanied declining mobility of Schwann cells as they engaged in the myelination of re-growing axons. These findings are the first to identify upregulated C6st1 gene expression correlating with the motility of Schwann cells that guide growing axons through both developmental and injured environments.
Department of Biochemistry, Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China.
Jun
J
Liu
Chi-Ho
CH
Chau
Hengying
H
Liu
Benjamin R
BR
Jang
Xiaoguang
X
Li
Ying-Shing
YS
Chan
Ying-Shang
YS
Chan
Daisy K Y
DK
Shum
D000818:Animals; D001369:Axons / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D019765:Chondroitin ABC Lyase / Q000494:pharmacology; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation; D000097811:Carbohydrate Sulfotransferases
D019765:Chondroitin ABC Lyase; D018076:DNA, Complementary; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases