Sialic Acid within the Glycosylphosphatidylinositol Anchor Targets the Cellular Prion Protein to Synapses

Bate, C and Nolan, W and McHale-Owen, H and Williams, A (2016) Sialic Acid within the Glycosylphosphatidylinositol Anchor Targets the Cellular Prion Protein to Synapses. JOURNAL OF BIOLOGICAL CHEMISTRY, 291 (33). pp. 17093-101.

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Abstract

Although the cellular prion protein (PrPC) is concentrated at synapses, the factors that target PrPC to synapses are not understood. Here we demonstrate that exogenous PrPC was rapidly targeted to synapses in recipient neurons derived from Prnp knock-out(0/0) mice. The targeting of PrPC to synapses was dependent upon both neuronal cholesterol concentrations and the lipid and glycan composition of its glycosylphosphatidylinositol (GPI) anchor. Thus, the removal of either an acyl chain or sialic acid from the GPI anchor reduced the targeting of PrPC to synapses. Isolated GPIs (derived from PrPC) were also targeted to synapses, as was IgG conjugated to these GPIs. The removal of sialic acid from GPIs prevented the targeting of either the isolated GPIs or the IgG-GPI conjugate to synapses. Competition studies showed that pretreatment with sialylated GPIs prevented the targeting of PrPC to synapses. These results are consistent with the hypothesis that the sialylated GPI anchor attached to PrPC acts as a synapse homing signal.