4.7 Article

Reconsideration of the Semaphorin-3A Binding Motif Found in Chondroitin Sulfate Using Galnac4s-6st-Knockout Mice

期刊

BIOMOLECULES
卷 10, 期 11, 页码 -

出版社

MDPI
DOI: 10.3390/biom10111499

关键词

chondroitin sulfate; proteoglycans; perineuronal net; extracellular matrix

资金

  1. Ministry of Education, Culture, Sports, Science, and Technology, Japan [23110003, 20H03386, 25460080]
  2. Grants-in-Aid for Scientific Research [25460080, 20H03386] Funding Source: KAKEN

向作者/读者索取更多资源

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.

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