Reconsideration of the Semaphorin-3A Binding Motif Found in Chondroitin Sulfate Using Galnac4s-6st-Knockout Mice
Year: 2020
Type: article
Abstract: The chondroitin sulfate (CS)-rich dense extracellular matrix surrounding neuron cell bodies and proximal dendrites in a mesh-like structure is called a perineuronal net (PNN). CS chains in PNNs control neuronal plasticity by binding to PNN effectors, semaphorin-3A (Sema3A) and orthodenticle homeobox 2. Sema3A recognizes CS-containing type-E disaccharide units (sulfated at O-4 and O-6 of N-acetylgalactosamine). Type-E disaccharide units are synthesized by N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST). In this study, we demonstrated that Sema3A accumulates in the PNNs surrounding parvalbumin cells, even in mice deficient in GalNAc4S-6ST. In addition, there were no differences in the number and structure of PNNs visualized by Cat316 antibody and Wisteria floribunda lectin, which recognize CS chains, between wild type and GalNAc4S-6ST knockout mice. Therefore, we re-examined the Sema3A binding motif found in CS chains using chemically synthesized CS tetrasaccharides. As a result, we found that non-sulfated GalNAc residues at the non-reducing termini of CS chains are required for the binding of Sema3A.
Source: Biomolecules
DOI: 10.3390/biom10111499
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,901
Awards: G3001622453, Structural diversity of perineuronal nets and its functions in neural plasticity, G539948665, Glycobiology in diseases arising from impaired synthesis of sulfated glycosaminoglycans, Dysregulation of Sulfated Glycosaminoglycan Biosynthesis is Implicated in Inflammatory Response, G6612981372, G6854079658, Understanding of the mechanisms of sulfated glycosaminoglycan synthesis and their functions, Biology of sugar-alcohol modification in glycan
OpenAlex ID: W3095533124
