The role of the prion protein membrane anchor in prion infection

Suzette A Priola1, Kristin L McNally

  • 1Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA. spriola@niaid.nih.gov

Prion
|September 30, 2009
PubMed

Insights

The prion protein's GPI anchor is not essential for forming abnormal prion protein but is crucial for persistent prion infection and cell-to-cell spread.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Infectious Diseases

Background:

  • Prion diseases involve abnormal prion protein (PrP) formation.
  • The role of the C-terminal glycophosphatidyl-inositol (GPI) anchor in PrP's function during disease is not fully understood.
  • Existing data on the GPI anchor's necessity in prion infection are contradictory.

Purpose of the Study:

  • To investigate the specific role of the GPI membrane anchor in prion protein formation and infection.
  • To clarify the GPI anchor's importance in the propagation of prion infectivity.

Main Methods:

  • Utilized an in vitro model system to study prion infection.
  • Compared prion protein formation and infection in the presence and absence of the GPI anchor.

Main Results:

  • The GPI anchor is not essential for the formation of abnormal prion protein within a cell.
  • However, the GPI anchor is necessary for establishing persistent prion infection.
  • Data suggest GPI-anchored PrP is vital for amplifying and spreading prion infectivity between cells.

Conclusions:

  • The GPI anchor plays a critical role in the cell-to-cell transmission of prion diseases.
  • While not required for initial misfolding, the anchor is essential for sustained prion propagation and infectivity spread.

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