Axonal Regeneration by Glycosaminoglycan

Like other biomolecules including nucleic acid and protein, glycan plays pivotal roles in various cellular processes. For instance, it modulates protein folding and stability, organizes extracellular matrix and tissue elasticity, and regulates membrane trafficking. In addition, cell-surface glycans are often utilized as entry receptors for viruses,including SARS-CoV-2. Nevertheless, its roles as ligands to specific surface receptors have not been well understood with a few exceptions such as selectins and siglecs. Recent reports have demonstrated that chondroitin sulfate and heparan sulfate, both of which are glycosaminoglycans, work as physiological ligands on their shared receptor, protein tyrosine phosphatase sigma (PTP sigma). These two glycans differentially determine the fates of neuronal axons after injury in our central nervous system. That is, heparan sulfate promotes axonal regeneration while chondroitin sulfate inhibits it, inducing dystrophic endbulbs at the axon tips. In our recent study, we demonstrated that the chondroitin sulfate (CS)-PTP sigma axis disrupted autophagy flux at the axon tips by dephosphorylating cortactin. In this minireview, we introduce how glycans work as physiological ligands and regulate their intracellular signaling, especially focusing on chondroitin sulfate.

Automated summary

Glycan, like nucleic acid and protein, plays crucial roles in cellular processes by regulating protein folding, extracellular matrix organization, and membrane trafficking. While cell-surface glycans are utilized by viruses as entry receptors, their roles as ligands to specific surface receptors are not well understood except for a few exceptions.