retrograde protein transport, ER to cytosol

Definition

Target type: biologicalprocess

The directed movement of unfolded or misfolded proteins from the endoplasmic reticulum to the cytosol through the translocon. [PMID:11994744]

Retrograde protein transport from the endoplasmic reticulum (ER) to the cytosol is a critical process that ensures proper cellular function and homeostasis. This pathway is primarily responsible for the retrieval of misfolded or unassembled proteins from the ER lumen back to the cytosol for degradation or refolding. This process is tightly regulated and involves several key components:

1. **Recognition of misfolded proteins:** Chaperone proteins within the ER lumen, such as BiP (binding immunoglobulin protein), recognize misfolded proteins. BiP binds to unfolded proteins and prevents their aggregation, potentially hindering proper folding.

2. **Translocation to the cytosol:** Misfolded proteins are then targeted for translocation back to the cytosol via the Sec61 translocon, a protein channel embedded in the ER membrane. This process involves the protein's N-terminus being exposed to the cytosolic side of the ER membrane.

3. **Ubiquitination:** Once in the cytosol, the misfolded proteins undergo ubiquitination, a process that involves the attachment of ubiquitin molecules to the protein. Polyubiquitination, the attachment of multiple ubiquitin molecules, serves as a signal for proteasomal degradation.

4. **Proteasomal degradation:** Ubiquitinated proteins are recognized by the proteasome, a large multi-protein complex responsible for degrading tagged proteins. The proteasome breaks down the misfolded protein into smaller peptides, preventing their accumulation and potential toxicity.

5. **ER-associated protein degradation (ERAD):** The entire process of retrograde transport from the ER to the cytosol for degradation is known as ERAD. This pathway is crucial for maintaining ER homeostasis, preventing the accumulation of misfolded proteins that can disrupt ER function and lead to cellular stress.

This process ensures that proteins that are unable to fold properly in the ER are removed from the secretory pathway and degraded, ultimately contributing to the overall health and functionality of the cell.'
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Proteins (2)

Compounds (28)