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Intercellular transfer of the cellular prion protein
Tong Liu1, Ruliang Li, Tao Pan
1Division of Neuropathology, Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
The Journal of Biological Chemistry
|October 3, 2002
Summary
Cellular prion protein (PrP(C)) can transfer between cells, especially when activated. This GPI-anchor dependent process may impact prion disease development.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- The cellular prion protein (PrP(C)) is a glycosylphosphatidylinositol (GPI)-anchored protein implicated in prion diseases.
- Understanding PrP(C) intercellular transfer is crucial for elucidating prion pathogenesis.
Purpose of the Study:
- To investigate the intercellular transfer of PrP(C) between human cell lines.
- To determine the mechanisms regulating PrP(C) transfer, including the role of GPI anchors and cellular activation.
Main Methods:
- Co-culture of PrP(C)-expressing neuroblastoma cells with PrP(C)-deficient erythroleukemia cells.
- Utilizing phorbol 12-myristate 13-acetate (PMA) to activate protein kinase C and induce cellular activation.
- Assessing PrP(C) transfer via direct cell-to-cell contact and evaluating the role of the GPI anchor.
Main Results:
- Minimal PrP(C) transfer occurred between non-activated cells.
- Efficient PrP(C) transfer was observed upon cellular activation with PMA.
- PrP(C) transfer necessitates the GPI anchor and direct cell-to-cell contact.
- Another GPI-anchored protein, CD90, also transferred between activated cells, indicating a general mechanism.
Conclusions:
- Intercellular transfer of GPI-anchored proteins, including PrP(C), is a regulated process dependent on GPI anchors and cellular activation.
- This transfer mechanism may play a significant role in the spread of prion diseases.