Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

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...
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...
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
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.
ER Retrieval Pathway01:45

ER Retrieval Pathway

In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
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...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Transdifferentiated BLaER1 cells as a genetically-tractable model to study the interaction of pathogenic fungi with macrophages.

Disease models & mechanisms·2026
Same author

p1/s1, a 3'-nucleotidase/nuclease, allows Leishmania major to circumvent host innate immune response mechanisms.

PLoS pathogens·2026
Same author

Autophagy selectively clears ER in TNF-α-induced muscle atrophy.

Autophagy reports·2026
Same author

Structuring of the yeast endolysosomal pathway by the Rab5 guanine nucleotide exchange factors Muk1 and Vps9.

Molecular biology of the cell·2026
Same author

The Novel MuRF2 Target SNX5 Regulates PKA Activity Through Stabilization of RI-α and Controls Myogenic Differentiation.

Journal of cachexia, sarcopenia and muscle·2025
Same author

Early regulation and alternative splicing dynamics in glucocorticoid muscle atrophy revealed by temporal omics in C2C12 myotubes.

American journal of physiology. Cell physiology·2025

Related Experiment Video

Updated: Jun 11, 2026

Visualization and Quantification of Endogenous Intra-Organelle Protein Interactions at ER-Mitochondria Contact Sites by Proximity Ligation Assays
08:27

Visualization and Quantification of Endogenous Intra-Organelle Protein Interactions at ER-Mitochondria Contact Sites by Proximity Ligation Assays

Published on: October 20, 2023

Protein dislocation from the ER.

Katrin Bagola1, Martin Mehnert, Ernst Jarosch

  • 1Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125 Berlin, Germany.

Biochimica Et Biophysica Acta
|July 6, 2010
PubMed
Summary

Misfolded proteins in the endoplasmic reticulum (ER) are targeted for degradation via ER-associated protein degradation (ERAD). A specialized machinery facilitates the extraction of these aberrant proteins from the ER for proteasomal breakdown.

More Related Videos

Visualization of Endoplasmic Reticulum Localized mRNAs in Mammalian Cells
10:24

Visualization of Endoplasmic Reticulum Localized mRNAs in Mammalian Cells

Published on: December 17, 2012

Purification of the Membrane Compartment for Endoplasmic Reticulum-associated Degradation of Exogenous Antigens in Cross-presentation
12:48

Purification of the Membrane Compartment for Endoplasmic Reticulum-associated Degradation of Exogenous Antigens in Cross-presentation

Published on: August 21, 2017

Related Experiment Videos

Last Updated: Jun 11, 2026

Visualization and Quantification of Endogenous Intra-Organelle Protein Interactions at ER-Mitochondria Contact Sites by Proximity Ligation Assays
08:27

Visualization and Quantification of Endogenous Intra-Organelle Protein Interactions at ER-Mitochondria Contact Sites by Proximity Ligation Assays

Published on: October 20, 2023

Visualization of Endoplasmic Reticulum Localized mRNAs in Mammalian Cells
10:24

Visualization of Endoplasmic Reticulum Localized mRNAs in Mammalian Cells

Published on: December 17, 2012

Purification of the Membrane Compartment for Endoplasmic Reticulum-associated Degradation of Exogenous Antigens in Cross-presentation
12:48

Purification of the Membrane Compartment for Endoplasmic Reticulum-associated Degradation of Exogenous Antigens in Cross-presentation

Published on: August 21, 2017

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Eukaryotic cells possess a quality control system in the endoplasmic reticulum (ER) to manage misfolded proteins.
  • Terminally misfolded proteins are targeted for dislocation into the cytosol and subsequent degradation by 26S proteasomes, a process known as ER-associated protein degradation (ERAD).

Purpose of the Study:

  • To review current understanding of the machinery responsible for extracting misfolded proteins from the ER during ERAD.
  • To explore the unique features and mechanisms of the ER dislocation apparatus that handles heterogeneous client proteins.

Main Methods:

  • Literature review of current research on ERAD and protein dislocation.
  • Analysis of the principles governing substrate recognition and transport across the ER membrane.
  • Discussion of the dynamic and flexible nature of the protein dislocation system.

Main Results:

  • ERAD substrates are recognized and extracted from the ER via mechanisms distinct from typical protein import pathways.
  • The ER dislocation system must accommodate partially folded and heavily glycosylated proteins without compromising ER integrity.
  • The transport machinery exhibits a dynamic and flexible nature to handle diverse aberrant polypeptides.

Conclusions:

  • The ER dislocation apparatus is a complex and adaptable system crucial for cellular protein homeostasis.
  • Understanding the mechanisms of ERAD substrate extraction is vital for comprehending cellular quality control and disease pathogenesis.
  • Further research into the dynamic nature of the dislocation machinery will illuminate novel therapeutic targets.