Gliosis of glial fibrillary acidic protein (GFAP) associated astrocytes is considered to be one of the hallmarks of transmissible spongiform encephalopathies (TSEs). In the present study, remarkable GFAP–PrPSc or GFAP–PrPC complexes were separately detected in the brain homogenates of 263 K (Scrapie)-infected or normal hamsters by co-immunoprecipitation assay. To get more exact molecular evidences for interaction between prion protein (PrP) and GFAP, various recombinant PrP or GFAP proteins were expressed using prokaryotic-expressing and in vitro translation system. Using pull down and co-immunoprecipitation assays, reliable molecular interaction between PrP and GFAP was observed, and proteinase K (PK)-digested PrPSc molecules were confirmed to be able to bind the recombinant GFAP specifically as well. The region within PrP that was responsible for interaction with GFAP was narrowed to PK-resistant core of PrP (i.e. aa 91–230). The study of the association of PrP with GFAP supplies the molecular evidence for the observation of co-localization of PrPSc and GFAP in the brains of TSEs and may further provide insight into a potential role of GFAP in the biological function of PrP and the pathogenesis of prion diseases.
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We thank Drs Chen Gao, Jian-Ming Chen and Chan Tian from State Key Laboratory for Infectious Disease Prevention and Control for helpful discussion. This work was supported by Chinese National Natural Science Foundation Grants 30571672 and 30500018, National Science and Technology Task Force Project (2006BAD06A13-2) and National Basic Research Program of China (973 Program) (2007CB310505).
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Dong, C., Wang, X., Wang, X. et al. Molecular interaction between prion protein and GFAP both in native and recombinant forms in vitro. Med Microbiol Immunol 197, 361–368 (2008). https://doi.org/10.1007/s00430-007-0071-0
- Prion protein
- Glial fibrillary acidic protein
- Transmissible spongiform encephalopathies
- Molecular interaction