Upregulation of chondroitin 6-sulphotransferase-1 facilitates Schwann cell migration during axonal growth

Abstract

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.

Manipulation of Schwann cell migration across the astrocyte boundary by polysialyltransferase-loaded superparamagnetic nanoparticles under magnetic field

“…[8][9][10] To solve this problem, SCs genetically modified to alter their adhesive properties have been investigated. [11][12][13] In vertebrates, the neural cell adhesion molecule (NCAM) is expressed on axonal and SC membranes, and its function is influenced by polysialylation, a critical mediator of neural cell migration. 12 Polysialic acid (PSA) is a linear homopolymer of α2,8-Nacetylneuraminic acid, which is synthesized on NCAM by polysialyltransferase (PST) and sialyltransferase X (STX).…”

6-Sulphated Chondroitins Have a Positive Influence on Axonal Regeneration

“…One study into injury-related CSST upregulation in the damaged cortex in rats found C6ST -1 (Accession: NM_016803.3) to be upregulated while another study showed increased 6 and 4,6-sulphated GAGs, and a third study of injured spinal cord found an increase in 4-sulphated GAG [21]–[22], [26]. C6ST -1 upregulation has been associated with Schwann cell-assisted guidance of axons through the developing and injured environment [27].…”

Cdc2-mediated Schwann cell migration during peripheral nerve regeneration

“…Of the molecular factors responsible for Schwann cell migration, NGF and its Schwann cell receptor (low-affinity NGF receptor or LNGFR) and 4C5 Schwann cell surface antigen were reported to mediate Schwann cell migration on denervated sciatic nerve (Anton et al, 1994a;Yfanti et al, 2004). Oxidized galectin-1, which is produced from Schwann cells and neurons and functions as a cytokine, and extracellular matrix components, such as laminin (merosin) and products of chondroitin 6-sulphotransferase activity, were reported to promote axonal regeneration by Schwann cell migration (Fukaya et al, 2003;Anton et al, 1994b;Liu et al, 2006). These studies implicate the importance of the molecular interaction of Schwann cells with the environment, but the events within the migrating Schwann cell in response to injury are largely unknown.…”