Related Experiment Video

Updated: Jul 31, 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

A transmembrane form of the prion protein contains an uncleaved signal peptide and is retained in the endoplasmic

R S Stewart1, B Drisaldi, D A Harris

  • 1Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110.

Molecular Biology of the Cell
|April 11, 2001
PubMed

Insights

Transmembrane prion protein (CtmPrP) is retained in the endoplasmic reticulum and degraded by the proteasome. This finding offers insights into prion disease mechanisms and cellular protein processing.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Prion diseases are linked to the infectious prion protein (PrPSc).
  • A transmembrane variant, (Ctm)PrP, is hypothesized to directly cause neurodegeneration.
  • Understanding (Ctm)PrP's cellular fate is crucial for elucidating disease pathogenesis.

Purpose of the Study:

  • To investigate the cellular behavior and fate of the transmembrane prion protein (Ctm)PrP.
  • To determine if (Ctm)PrP is directly involved in prion-associated neurodegeneration.
  • To explore the mechanisms controlling membrane protein topology.

Main Methods:

  • Utilized a mutant prion protein (PrP) engineered for exclusive (Ctm)PrP topology.
  • Analyzed protein localization and degradation pathways within the endoplasmic reticulum.
  • Characterized the structural features of (Ctm)PrP, including signal peptides and anchors.

Main Results:

  • The exclusively synthesized (Ctm)PrP mutant was retained within the endoplasmic reticulum.
  • (Ctm)PrP was found to be degraded via the proteasome pathway.
  • The study confirmed the presence of an uncleaved N-terminal signal peptide and a C-terminal glycolipid anchor in (Ctm)PrP.

Conclusions:

  • The endoplasmic reticulum retention and proteasomal degradation of (Ctm)PrP provide insights into its cellular processing.
  • These findings suggest potential cellular pathways through which (Ctm)PrP may contribute to prion disease.
  • The study enhances understanding of general mechanisms governing membrane protein topology during synthesis.

More Related Videos

Purification and Refolding to Amyloid Fibrils of (His)6-tagged Recombinant Shadoo Protein Expressed as Inclusion Bodies in E. coli09:43

Purification and Refolding to Amyloid Fibrils of (His)6-tagged Recombinant Shadoo Protein Expressed as Inclusion Bodies in E. coli

Published on: December 19, 2015

Reconstitution of Msp1 Extraction Activity with Fully Purified Components05:52

Reconstitution of Msp1 Extraction Activity with Fully Purified Components

Published on: August 10, 2021

Related Concept Videos

Directing Proteins to the Rough Endoplasmic Reticulum01:34

Directing Proteins to the Rough Endoplasmic Reticulum

The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
Cotranslational Protein Translocation01:20

Cotranslational Protein Translocation

Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
Insertion of Single-pass Transmembrane Proteins in the RER01:26

Insertion of Single-pass Transmembrane Proteins in the RER

Integral membrane proteins are proteins adhered to the lipid bilayer of a cell organelle or membrane. They can be of two types: transmembrane integral proteins that span the lipid bilayer and monotopic proteins that are attached to either side of the membrane but do not pass through it.
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...
Insertion of Multi-pass Transmembrane Proteins in the RER01:29

Insertion of Multi-pass Transmembrane Proteins in the RER

The rough ER membrane synthesizes, assembles, and embeds transmembrane proteins in diverse topologies. These proteins function as transporters or channels and can remain in the ER membrane or are sent to the Golgi complex, lysosome, and cell membrane.
The multipass transmembrane proteins are the type IV integral membrane proteins with multiple topogenic sequences determining their spatial arrangement in the ER membrane. Nearly all multipass proteins lack a cleavable signal sequence and use...
Post-translational Translocation of Proteins to the RER01:27

Post-translational Translocation of Proteins to the RER

A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
Protein Translocation Machinery on the ER Membrane01:28

Protein Translocation Machinery on the ER Membrane

The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the translocon complex.