Interaction of receptor type of protein tyrosine phosphatase sigma (RPTPσ) with a glycosaminoglycan library

Abstract

Receptor type of protein tyrosine phosphatase sigma (RPTPσ) functions as a glycosaminoglycan (GAG) receptor of neuronal cells in both the central and peripheral nervous systems. Both chondroitin sulphate (CS) and heparan sulphate (HS) are important constituents of GAG ligands for RPTPσ, although they have opposite effects on neuronal cells. CS inhibits neurite outgrowth and neural regeneration through RPTPσ, whereas HS enhances them. We prepared recombinant RPTPσ N-terminal fragment containing the GAG binding site and various types of biotin-conjugated GAG (CS and HS) with chemical modification and chemo-enzymatic synthesis. Then interaction of the RPTPσ N-terminal fragment was analysed using GAG-biotin immobilized on streptavidin sensor chips by surface plasmon resonance. Interaction of RPTPσ with the CS library was highly correlated to the degree of disulphated disaccharide E unit, which had two sulphate groups at C-4 and C-6 positions of the N-acetylgalactosamine residue (CSE). The optimum molecular mass of CSE was suggested to be approximately 10 kDa. Heparin showed higher affinity to RPTPσ than the CS library. Our GAG library will not only contribute to the fields of carbohydrate science and cell biology, but also provide medical application to regulate neural regeneration.

PTPσ Knockdown in Lampreys Impairs Reticulospinal Axon Regeneration and Neuronal Survival After Spinal Cord Injury

“…Moreover, the sulphation patterns on the CSPG GAG side chains are believed to greatly influence receptor interactions. Notably, PTPσ has been shown to preferentially interact with di-sulfated CSPGs and only weakly interact with mono-sulfated CSPGs, including CS-C, the dominant CSPG species in the glial scar (Katagiri et al, 2018;Tadai et al, 2018). While CSPGs in the mammalian glial scar may contain sufficient GAG diversity to preserve PTPσ binding, CSPGs in lampreys remain largely uncharacterized.…”