Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
EMBO J. 2010 Feb 17;29(4):782-94. doi: 10.1038/emboj.2009.392. Epub 2010 Jan 7.

GPI anchoring facilitates propagation and spread of misfolded Sup35 aggregates in mammalian cells.

Author information

  • 1National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Laboratory of Persistent Viral Diseases, Hamilton, MT 59840, USA.

Abstract

Prion diseases differ from other amyloid-associated protein misfolding diseases (e.g. Alzheimer's) because they are naturally transmitted between individuals and involve spread of protein aggregation between tissues. Factors underlying these features of prion diseases are poorly understood. Of all protein misfolding disorders, only prion diseases involve the misfolding of a glycosylphosphatidylinositol (GPI)-anchored protein. To test whether GPI anchoring can modulate the propagation and spread of protein aggregates, a GPI-anchored version of the amyloidogenic yeast protein Sup35NM (Sup35GPI) was expressed in neuronal cells. Treatment of cells with Sup35NM fibrils induced the GPI anchor-dependent formation of self-propagating, detergent-insoluble, protease-resistant, prion-like aggregates of Sup35GPI. Live-cell imaging showed intercellular spread of Sup35GPI aggregation to involve contact between aggregate-positive and aggregate-negative cells and transfer of Sup35GPI from aggregate-positive cells. These data demonstrate GPI anchoring facilitates the propagation and spread of protein aggregation and thus may enhance the transmissibility and pathogenesis of prion diseases relative to other protein misfolding diseases.

PMID:
20057357
[PubMed - indexed for MEDLINE]
PMCID:
PMC2829165
Free PMC Article

Images from this publication.See all images (6)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk