3-O-sulfated Heparan Sulfate Interactors Target Synaptic Adhesion Molecules from Neonatal Mouse Brain and Inhibit Neural Activity and Synaptogenesis in Vitro
Authors
Affiliations
Heparan sulfate (HS) chains, covalently linked to heparan sulfate proteoglycans (HSPG), promote synaptic development and functions by connecting various synaptic adhesion proteins (AP). HS binding to AP could vary according to modifications of HS chains by different sulfotransferases. 3-O-sulfotransferases (Hs3sts) produce rare 3-O-sulfated HSs (3S-HSs), of poorly known functions in the nervous system. Here, we showed that a peptide known to block herpes simplex virus by interfering with 3S-HSs in vitro and in vivo (i.e. G2 peptide), specifically inhibited neural activity, reduced evoked glutamate release, and impaired synaptic assembly in hippocampal cell cultures. A role for 3S-HSs in promoting synaptic assembly and neural activity is consistent with the synaptic interactome of G2 peptide, and with the detection of Hs3sts and their products in synapses of cultured neurons and in synaptosomes prepared from developing brains. Our study suggests that 3S-HSs acting as receptors for herpesviruses might be important regulators of neuronal and synaptic development in vertebrates.
Spildrejorde M, Samara A, Sharma A, Leithaug M, Falck M, Modafferi S iScience. 2023; 26(10):107755.
PMID: 37731623 PMC: 10507163. DOI: 10.1016/j.isci.2023.107755.
Ferreira A, Timmerman E, Staes A, Vuylsteke M, De Muynck L, Gevaert K Sci Data. 2023; 10(1):121.
PMID: 36879013 PMC: 9986659. DOI: 10.1038/s41597-023-02009-1.
Hayes A, Melrose J Int J Mol Sci. 2023; 24(2).
PMID: 36674659 PMC: 9867265. DOI: 10.3390/ijms24021148.
Proteoglycan Sulphation in the Function of the Mature Central Nervous System.
Fawcett J, Kwok J Front Integr Neurosci. 2022; 16:895493.
PMID: 35712345 PMC: 9195417. DOI: 10.3389/fnint.2022.895493.
Patel V, Pineda D, Berenstein E, Hauser B, Choi S, Prochazkova M Matrix Biol. 2021; 103-104:37-57.
PMID: 34653670 PMC: 8629026. DOI: 10.1016/j.matbio.2021.10.002.