title: Ran-2, a glial lineage marker, is a GPI-anchored form of ceruloplasmin.
abstract: Cell interactions in the nervous system are frequently mediated by surface proteins that are attached to the membrane by a glycosyl phosphatidylinositol (GPI) anchor. In this study, we have characterized the expression of such proteins on glial cells. We have detected a major GPI-anchored protein on astrocytes and Schwann cells, with a molecular weight of 140 kD. When Schwann cells were treated with forskolin to promote a myelinating phenotype, expression of this 140-kD protein dramatically decreased, whereas another GPI-anchored protein of 80 kD was strongly induced; expression of other integral membrane proteins were likewise 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 immunoprecipitating this 140-kD protein with the Ran-2 monoclonal antibody. The Ran-2 antigen is expressed over the entire Schwann cell surface in a punctate fashion; it is removed by phosphatidylinositol phospholipase C treatment, 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 downregulated. Protein sequencing of the Ran-2 antigen immunopurified from rat brain membranes showed complete identity over two extended segments with the copper binding protein ceruloplasmin. These findings indicate that astrocytes and Schwann cells express a novel GPI-anchored form of ceruloplasmin and suggest that this GPI form plays a role in axonal-glial interactions.
authors.affiliation: Department of Cell Biology, Kaplan Cancer Center, New York University Medical School, New York 10016, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Salzer
authors.forename: L
authors.initials: L
authors.lastname: Lovejoy
authors.forename: M C
authors.initials: MC
authors.lastname: Linder
authors.forename: C
authors.initials: C
authors.lastname: Rosen
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000187:drug effects; D015415:Biomarkers / Q000737:chemistry; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D002570:Ceruloplasmin / Q000032:analysis*; D018920:Coculture Techniques; D005576:Colforsin / Q000494:pharmacology; D017261:Glycosylphosphatidylinositols / Q000032:analysis*; D006825:Hybridomas; D008565:Membrane Proteins / Q000032:analysis; D009457:Neuroglia / Q000737:chemistry / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D020033:Protein Isoforms / Q000032:analysis*; D051381:Rats; D012583:Schwann Cells / Q000737:chemistry / Q000187:drug effects
chemical_list: D015415:Biomarkers; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; D020033:Protein Isoforms; D005576:Colforsin; D002570:Ceruloplasmin