Spreading of a prion domain from cell-to-cell by vesicular transport in Caenorhabditis elegans

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Updated: May 6, 2026

Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans
12:57

Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans

Published on: January 8, 2015

15.7K

Carmen I Nussbaum-Krammer1, Kyung-Won Park, Liming Li

  • 1Department of Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, Evanston, Illinois, United States of America.

Plos Genetics
|April 5, 2013
PubMed

Insights

This study introduces a new model in C. elegans to study prion protein propagation. The yeast prion domain NM causes toxicity and spreads between cells via autophagy, disrupting proteostasis.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Genetics

Background:

  • Prion proteins adopt self-propagating conformations, causing transmissible spongiform encephalopathies and potentially contributing to neurodegenerative diseases like Alzheimer's and Parkinson's.
  • Studying the cell-to-cell transmission of misfolded, aggregation-prone proteins is crucial for understanding these diseases, but limited animal models exist.
  • The yeast prion protein Sup35 contains a prion domain (NM) whose aggregation and toxicity are influenced by repeat length.

Purpose of the Study:

  • To establish a new metazoan model in Caenorhabditis elegans for studying prion protein propagation.
  • To investigate the prion-like properties and transmission mechanisms of the yeast Sup35 prion domain (NM) in a multicellular organism.
  • To explore the role of the autophagy-lysosome pathway in the intercellular spread of aggregation-prone proteins.

Main Methods:

  • Expression of the yeast Sup35 prion domain (NM) in the nematode Caenorhabditis elegans.
  • Analysis of NM aggregation, toxicity, and localization using microscopy.
  • Assessment of cellular and organismal defects, including mitochondrial integrity, development, and proteostasis.

Main Results:

  • The NM prion domain forms toxic aggregates in C. elegans, with toxicity dependent on repeat length.
  • NM aggregates co-localize with autophagy-related vesicles, facilitating cell-to-cell transmission.
  • Expression of NM leads to mitochondrial dysfunction, developmental arrest, tissue defects, and loss of proteostasis in a cell-autonomous and non-autonomous manner.
  • The autophagy-lysosome pathway is involved in the transmission of cytosolic aggregation-prone proteins between tissues.

Conclusions:

  • The Sup35 prion domain exhibits prion-like behavior in the multicellular organism C. elegans.
  • Autophagy-lysosome pathway mediates the intercellular transmission of cytosolic aggregation-prone proteins.
  • This C. elegans model provides a valuable system for studying the mechanisms of prion propagation and related neurodegenerative diseases.

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