Translocation
Translocation of proteins occurs either during translation (co-translational translocation) or after translation (post-translational translocation) and depends on the N'-terminal signal-recognition particle (SRP). The SRP interacts with a SRP receptor on the ER and promotes transport of proteins into the ER lumen where they are prepared for secretion.
| Cat. No. | Product Name / Activity |
|---|---|
| 1231 | Brefeldin A |
| Disrupts protein translocation to Golgi | |
| 5153 | ML 240 |
| ATP-competitive inhibitor of p97 ATPase | |
| 6180 | NMS 873 |
| Potent and selective p97 ATPase (VCP) allosteric inhibitor |
Protein translocation is the process of transporting proteins across or into a cellular membrane. Translocation involves the target protein identification through the N’-terminal signal-recognition particle (SRP), the interaction of the SRP with the signal receptor and translocon, the movement of the target protein across the membrane, and folding and regulating the protein within the membrane. Translocation can occur either during co- or post-translation of the target protein.
Translocons are channels which facilitate translocation across the cellular membrane. There are two main classes of translocons: signal gated and signal assembled. Signal gated systems are composed of static translocons which transport unfolded proteins across a membrane in response to an SRP, while signal assembled systems utilize dynamic translocons to transport fully folded proteins. Signal gated translocation can occur with co- or post-translational proteins, whereas signal assembled translocation is only utilized for post-translational proteins.
Molecular chaperones are essential in translocation by maintaining unfolded proteins prior to transport, regulating transport direction, and identifying mis-folded proteins for degradation.
Protein translocation has been most thoroughly studied in the endoplasmic reticulum (ER) of eukaryotic cells but occurs across other cellular membranes, including those of prokaryotic cells.
The ER has its own regulatory system, including the ER associated protein degradation (ERAD) and the unfolded protein response. ERAD recognizes and retrotranslocates mis-folded proteins to the cytosol for ubiquitination. The unfolded protein response (UPR) to atypical proteins includes increasing ERAD expression factors, facilitating folding via molecular chaperones, and transporting them to other parts of the cell. The ERAD and UPR regulatory responses can be influenced by inhibitors such as NMS 873 (Cat. No. 6180) and ML 240 (Cat. No. 5153).
Errors in protein translocation can contribute to a variety of diseases. Within the mitochondria, changes in translocation pathways are associated with cancer, diabetes, and neurodegenerative diseases such as Mohr Tranebjaerg syndrome and Alzheimer’s disease. Mistakes in protein folding can also contribute to diseases including cystic fibrosis and Parkinson’s disease.