| First Author | Stewart RS | Year | 2005 |
| Journal | J Biol Chem | Volume | 280 |
| Issue | 16 | Pages | 15855-64 |
| PubMed ID | 15671025 | Mgi Jnum | J:128889 |
| Mgi Id | MGI:3768228 | Doi | 10.1074/jbc.M412298200 |
| Citation | Stewart RS, et al. (2005) A transmembrane form of the prion protein is localized in the Golgi apparatus of neurons. J Biol Chem 280(16):15855-64 |
| abstractText | (Ctm)PrP is a transmembrane version of the prion protein that has been proposed to be a neurotoxic intermediate underlying prion-induced pathogenesis. In previous studies, we found that PrP molecules carrying mutations in the N-terminal signal peptide (L9R) and the transmembrane domain (3AV) were synthesized exclusively in the (Ctm)PrP form in transfected cell lines. To characterize the properties of (Ctm)PrP in a neuronal setting, we have utilized cerebellar granule neurons cultured from Tg(L9R-3AV) mice that developed a fatal neurodegenerative illness. We found that about half of the L9R-3AV PrP synthesized in these neurons represents (Ctm)PrP, with the rest being (Sec)PrP, the glycolipid anchored form that does not span the membrane. Both forms contained an uncleaved signal peptide, and they are differentially glycosylated. (Sec)PrP was localized on the surface of neuronal processes. Most surprisingly, (Ctm)PrP was concentrated in the Golgi apparatus, rather in the endoplasmic reticulum as it is in transfected cell lines. Our study is the first to analyze the properties of (Ctm)PrP in a neuronal context, and our results suggest new hypotheses about how this form may exert its neurotoxic effects. |
