RAN-2, A GLIAL LINEAGE MARKER, IS A GPI-ANCHORED FORM OF CERULOPLASMIN

Cell interactions in the nervous system are frequently mediated by sur face proteins that are attached to the membrane by a glycosyl phosphat idylinositol (GPI) anchor. In this study, we have characterized the ex pression of such proteins on glial cells. We have detected a major GPI -anchored protein on astrocytes and Schwann cells, with a molecular we ight of 140 kD. When Schwann cells were treated with forskolin to prom ote a myelinating phenotype, expression of this 140-kD protein dramati cally decreased, whereas another GPI-anchored protein of 80 kD was str ongly induced; expression of other integral membrane proteins were lik ewise dramatically altered. The size and pattern of expression of the 140-kD protein suggested that it might correspond to the Ran-2 antigen , a glial lineage marker. This notion was confirmed by immunoprecipita ting this 140-kD protein with the Ran-2 monoclonal antibody. The Ran-2 antigen is expressed over the entire Schwann cell surface in a puncta te fashion; it is removed by phosphatidylinositol phospholipase C trea tment, thereby confirming that it is GPI-anchored, When Schwann cells are cocultured with neurons, the Ran-2 antigen initially concentrates at sites of Schwann cell contact with neurons, suggesting that it may play a role in early Schwann cell-neuron interactions; it is then down regulated, Protein sequencing of the Ran-2 antigen immunopurified from rat brain membranes showed complete identity over two extended segmen ts with the copper binding protein ceruloplasmin. These findings indic ate that astrocytes and Schwann cells express a novel GPI-anchored for m of ceruloplasmin and suggest that this GPI form plays a role in axon al-glial interactions. J. Neurosci. Res. 54:147-157, 1998. (C) 1998 Wi ley-Liss, Inc.