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Related Concept Videos

ER Retrieval Pathway01:45

ER Retrieval Pathway

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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...
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Directing Proteins to the Rough Endoplasmic Reticulum01:34

Directing Proteins to the Rough Endoplasmic Reticulum

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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...
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Tail-anchoring of Proteins in the ER Membrane01:45

Tail-anchoring of Proteins in the ER Membrane

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Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
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Post-translational Translocation of Proteins to the RER01:27

Post-translational Translocation of Proteins to the RER

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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...
5.4K
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

3.4K
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...
3.4K
Protein Translocation Machinery on the ER Membrane01:28

Protein Translocation Machinery on the ER Membrane

4.3K
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...
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Related Experiment Video

Updated: Jun 19, 2026

The MultiBac Protein Complex Production Platform at the EMBL
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The MultiBac Protein Complex Production Platform at the EMBL

Published on: July 11, 2013

Protein targeting to the ER membrane: multiple pathways and shared machinery.

Wendy N Sánchez1,2,3, Arnold J M Driessen1, Christian A M Wilson2

  • 1Department of Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, Faculty of Science and Engineering, University of Groningen, Groningen, The Netherlands.

Critical Reviews in Biochemistry and Molecular Biology
|May 16, 2025
PubMed
Summary

Protein targeting to the endoplasmic reticulum (ER) involves complex pathways. This review details the molecular mechanisms of ER protein targeting, focusing on the Sec61 complex and its accessory factors.

Keywords:
Protein targetingendoplasmic reticulumsec61 complexsignal peptidesignal recognition particletranslocon

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Last Updated: Jun 19, 2026

The MultiBac Protein Complex Production Platform at the EMBL
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Purification of the Membrane Compartment for Endoplasmic Reticulum-associated Degradation of Exogenous Antigens in Cross-presentation
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Escherichia coli-Based Cell-Free Protein Synthesis: Protocols for a robust, flexible, and accessible platform technology

Published on: February 25, 2019

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The endoplasmic reticulum (ER) is crucial for protein synthesis and processing in eukaryotic cells.
  • Approximately one-third of the cellular proteome is handled by the ER.
  • Protein entry into the ER occurs via both co-translational and post-translational pathways.

Purpose of the Study:

  • To review the molecular mechanisms of protein targeting to the ER.
  • To highlight the roles of the Sec61 complex and associated factors.
  • To discuss recent advances in understanding ER protein translocation.

Main Methods:

  • Literature review of protein targeting mechanisms.
  • Analysis of the Sec61 complex structure and function.
  • Integration of findings on cytosolic factors and RNA-based targeting.

Main Results:

  • Protein targeting to the ER is achieved through diverse pathways, including signal peptide recognition and RNA-mediated mechanisms.
  • The Sec61 complex is central to protein translocation, exhibiting dynamic conformational changes.
  • Numerous accessory factors modulate the efficiency and specificity of ER protein entry.

Conclusions:

  • ER protein targeting is a highly regulated and complex process.
  • Recent discoveries reveal intricate details of translocation machinery dynamics.
  • Understanding these pathways is vital for comprehending cellular protein homeostasis.