NG2 cells comprise a heterogeneous precursor population but molecular markers distinguishing between the assumed NG2 cell subpopulations are lacking. Previously, we described that a subfraction of the synaptic cell adhesion molecule SynCAM 1 is modified with the glycan polysialic acid (polySia) in NG2 cells. As for its major carrier, the neural cell adhesion molecule NCAM, polySia attenuates SynCAM 1 adhesion. Functions, as well as cellular and subcellular distribution of polySia-SynCAM 1 are elusive. Using murine glial cultures we now demonstrate that polySia-SynCAM 1 is confined to the Golgi compartment of a subset of NG2 cells and transiently recruited to the cell surface in response to depolarization. NG2 cells with Golgi-confined polySia were NCAM-negative, but positive for markers of oligodendrocyte precursor cells (OPCs). Consistent with previous data on polySia-SynCAM 1, polySia in Ncam(-/-) NG2 cells was exclusively attached to N-glycans and synthesized by ST8SIA2, one out of two mammalian polysialyltransferases. Unexpectedly, Golgi-confined polySia was also detected in Ncam(-/-) microglia, but this fraction resided on O-glycans and was produced by the second polysialyltransferase, ST8SIA4, indicating the presence of yet another polySia carrier in microglia. Searching for this carrier, we identified polysialylated neuropilin-2, so far only known from dendritic cells and exudate macrophages. Microglia activation by LPS, but not interleukin-4, caused a transient translocation of Golgi-localized polySia to the cell surface, resulting in complete depletion. Finally, NO-production of LPS-stimulated microglia was attenuated by addition of polySia suggesting that the observed loss of polySia-neuropilin-2 is involved in negative feedback regulation of pro-inflammatory microglia polarization.
Keywords: PSA-NCAM; microglia activation; oligodendrocyte precursor cell; protein glycosylation.
© 2015 Wiley Periodicals, Inc.