Abstract
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 (PTPσ). 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)-PTPσ 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.
Highlights
The human neural circuit, composed of the central nervous system (CNS) and the peripheral nervous system (PNS), reaches approximately 1 million km and is formed mainly by neural axons
To link the PTPσ-autophagy axis, we focused on finding the specific substrate for PTPσ that is involved at the fusion step between autophagosomes and lysosomes (Sakamoto et al, 2019)
In a recent study we prepared a library of heparan sulfate (HS) octasaccharides and found that, through these octasaccharides together with chondroitin sulfate (CS) octasaccharides, PTPσ preferentially interacts with CS-E, a rare sulfation pattern in the natural CS chain, as well as with most HS oligomers bearing sulfate and sulfamate groups
Summary
Reviewed by: Shinji Miyata, Tokyo University of Agriculture and Technology, Japan Jerry Silver, Case Western Reserve University, United States. Like other biomolecules including nucleic acid and protein, glycan plays pivotal roles in various cellular processes. 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 (PTPσ). These two glycans differentially determine the fates of neuronal axons after injury in our central nervous system. We demonstrated that the chondroitin sulfate (CS)-PTPσ 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
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