Polysialylation of the Synaptic Cell Adhesion Molecule 1 (SynCAM 1) Depends Exclusively on the Polysialyltransferase ST8SiaII in Vivo

Abstract

Background: Polysialic acid is a developmentally regulated posttranslational modification. Results: Loss of the polysialyltransferase ST8SiaII but not ST8SiaIV abolished polysialylation of SynCAM 1 in the mouse brain. Conclusion: Polysialylation of SynCAM 1 is mediated by ST8SiaII throughout postnatal mouse brain development. Significance: Studying the molecular requirements for protein polysialylation is crucial for understanding how this process is regulated.

Polysialic Acid on Neuropilin-2 Is Exclusively Synthesized by the Polysialyltransferase ST8SiaIV and Attached to Mucin-type O-Glycans Located between the b2 and c Domain

“…mice, and in cell culture experiments, SynCAM 1 was efficiently polysialylated by ST8SiaII but served only as a poor substrate for ST8SiaIV (56). Here, we now showed that in contrast to SynCAM 1, NRP2 is a substrate for ST8SiaIV but not for ST8SiaII.…”

“…Beyond NCAM polysialylation, however, the two polysialyltransferases may exert very different functions by targeting distinct acceptor proteins. Recently, we showed that polysialylation of SynCAM 1 strictly depends on the presence of ST8SiaII (56). In the developing brain, the modification of SynCAM 1 by polySia is cell type-specific and restricted to NG2 cells, a class of multifunctional precursor cells (33,57).…”

Polysialic acid modification of the synaptic cell adhesion molecule SynCAM 1 in human embryonic stem cell-derived oligodendrocyte precursor cells

“…Total RNA from hESCd-OPCs was extracted using NucleoSpin RNA II kit (Macherey-Nagel) and reverse transcribed as described (Rollenhagen et al, 2012). Quantitative real-time PCR was performed as described previously (Konze et al, 2014).…”

“…And because polySia attenuates adhesive interactions, it has been proposed that polysialylation of SynCAM 1 modulates the assembly or disassembly of neuron-NG2 cell synapses (Galuska et al, 2010). However, many aspects of OPC biology differ fundamentally between mice and humans (Sim et al, 2009) and so far, the polySia modification of SynCAM 1 has only been shown in mice (Galuska et al, 2010;Rollenhagen et al, 2012). Therefore, the present study was designed to assess polySia acceptors in human OPCs generated from ESCs.…”

“…Both enzymes show high acceptor specificity and therefore polySia is restricted to only few carrier molecules (Mühlenhoff et al, 2013). In addition to the major polySia carrier NCAM, we recently described the ST8SIA2-mediated polysialylation of a fraction of the synaptic cell adhesion molecule SynCAM 1 within a subset of NG2 cells of the early postnatal mouse brain (Galuska et al, 2010;Rollenhagen et al, 2012). NG2 cells are able to communicate with neurons via specialized neuron-NG2 cell synapses (Bergles et al, 2000;Karadottir et al, 2005;Kukley et al, 2007;Etxeberria et al, 2010).…”