Related Experiment Video
Updated: Sep 24, 2025
10:24
Visualization of Endoplasmic Reticulum Localized mRNAs in Mammalian Cells
Published on: December 17, 2012
14.4K
A 'NAC' for targeting proteins to the ER
João P L Coelho1, Sichen Shao1
1Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Trends in Biochemical Sciences
|May 2, 2022
Summary
The ribosome-associated complex (NAC) unexpectedly senses endoplasmic reticulum (ER) targeting signals. This complex recruits the signal recognition particle (SRP) for accurate protein targeting to the ER.
Area of Science:
- Molecular Biology
- Cell Biology
- Protein Trafficking
Background:
- The signal recognition particle (SRP) mediates cotranslational targeting of proteins to the endoplasmic reticulum (ER).
- Accurate protein localization is crucial for cellular function and homeostasis.
Purpose of the Study:
- To investigate the role of the ribosome-bound nascent chain-associated complex (NAC) in protein targeting to the ER.
- To elucidate the mechanism by which NAC interacts with SRP and ER-targeting signals.
Main Methods:
- Biochemical assays to study protein-RNA and protein-protein interactions.
- In vitro reconstitution of protein targeting pathways.
- Analysis of nascent polypeptide chains and their association with targeting factors.
Main Results:
- NAC functions as a sensor for ER-targeting signals on nascent polypeptides.
- NAC actively recruits SRP to ribosomes engaged with ER-bound proteins.
- This interaction ensures high-fidelity targeting of proteins to the ER.
Conclusions:
- NAC plays a critical, previously unrecognized role in the SRP-mediated protein targeting pathway.
- NAC acts as a crucial intermediary, ensuring efficient and accurate delivery of proteins to the ER.
More Related Videos
Related Concept Videos
01:34Directing Proteins to the Rough Endoplasmic Reticulum
9.2K
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...
9.2K
01:28Protein Translocation Machinery on the ER Membrane
5.0K
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...
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...
5.0K
01:34Nuclear Protein Sorting
4.8K
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
4.8K
01:32Export of Misfolded Proteins out of the ER
4.0K
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...
4.0K
01:45Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
01:45Tail-anchoring of Proteins in the ER Membrane
3.2K
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...
3.2K