Sialic Acid within the Glycosylphosphatidylinositol Anchor Targets the Cellular Prion Protein to Synapses.
Although the cellular prion protein (PrP(C)) is concentrated at synapses, the factors that target PrP(C) to synapses are not understood. Here we demonstrate that exogenous PrP(C) was rapidly targeted to synapses in recipient neurons derived from Prnp knock-out((0/0)) mice. The targeting of PrP(C) 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 PrP(C) to synapses. Isolated GPIs (derived from PrP(C)) 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 PrP(C) to synapses. These results are consistent with the hypothesis that the sialylated GPI anchor attached to PrP(C) acts as a synapse homing signal.
From the Department of Pathology and Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, Herts AL9 7TA and.
Clive
C
Bate
From the Department of Pathology and Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, Herts AL9 7TA and.
William
W
Nolan
From the Department of Pathology and Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, Herts AL9 7TA and.
Harriet
H
McHale-Owen
the Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 OES, United Kingdom aw510@cam.ac.uk.
Alun
A
Williams
D000818:Animals; D002478:Cells, Cultured; D051379:Mice; D018345:Mice, Knockout; D019158:N-Acetylneuraminic Acid / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009844:Oligosaccharides / Q000235:genetics / Q000378:metabolism*; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D013570:Synaptic Membranes / Q000235:genetics / Q000378:metabolism*
C559297:(6-O-aminoethylphosphonato-mannopyranosyl)-(1-2)-mannopyranosyl-(1-6)-mannopyranosyl-(1-4)-(2-amino-2-deoxyglucopyranosyl)-(1-6)-1-O-(1,2-di-O-octadecanoyl-sn-glyceryl-phosphonato)-myo-inositol; D009844:Oligosaccharides; D018621:PrPC Proteins; D019158:N-Acetylneuraminic Acid
cholesterol; glycosylphosphatidylinositol (GPI anchor); prion; sialic acid; synapse