| First Author | Nunziante M | Year | 2003 |
| Journal | J Biol Chem | Volume | 278 |
| Issue | 6 | Pages | 3726-34 |
| PubMed ID | 12431994 | Mgi Jnum | J:81691 |
| Mgi Id | MGI:2449840 | Doi | 10.1074/jbc.M206313200 |
| Citation | Nunziante M, et al. (2003) Essential Role of the Prion Protein N Terminus in Subcellular Trafficking and Half-life of Cellular Prion Protein. J Biol Chem 278(6):3726-34 |
| abstractText | Aberrant metabolism and conformational alterations of the cellular prion protein (PrP(c)) are the underlying causes of transmissible spongiform encephalopathies in humans and animals. In cells, PrP(c) is modified post-translationally and transported along the secretory pathway to the plasma membrane, where it is attached to the cell surface by a glycosylphosphatidylinositol anchor. In surface biotinylation assays we observed that deletions within the unstructured N terminus of murine PrP(c) led to a significant reduction of internalization of PrP after transfection of murine neuroblastoma cells. Truncation of the entire N terminus most significantly inhibited internalization of PrP(c). The same deletions caused a significant prolongation of cellular half-life of PrP(c) and a delay in the transport through the secretory pathway to the cell surface. There was no difference in the glycosylation kinetics, indicating that all PrP constructs equally passed endoplasmic reticulum-based cellular quality control. Addition of the N terminus of the Xenopus laevis PrP, which does not encode a copper-binding repeat element, to N-terminally truncated mouse PrP restored the wild type phenotype. These results provide deeper insight into the life cycle of the PrP(c), raising the novel possibility of a targeting function of its N-proximal part by interacting with the secretory and the endocytic machinery. They also indicate the conservation of this targeting property in evolution. |
