Where to? — How Newly-Translated Proteins Find Their New Cellular Homes
Protein targeting is the phenomenon by which proteins are targeted (either during or after translation) to a destination such as a membrane-bound organelle, the cell membrane, or outside the cell. These mechanisms are most sophisticated and diverse in eukaryotes due to the presence of organelles, but even prokaryotes have similar targeting systems.
There exist different targeting signal locations on the protein for different organelles. For example, for the cell to target a protein to the mitochondrion, ER, or chloroplasts, an N-terminal sequence is needed. To target proteins to peroxisomes, a C-terminal sequence is needed.
Protein synthesis begins in the cytosol. Signals at various times during and after this process cause targeting. One example is targeting facilitated by signal recognition particle (SRP), which designates proteins to go to the endoplasmic reticulum (ER). While the mRNA is being translated, a signal sequence on the mRNA is translated into a signal peptide (towards the amino/5'/initially translated end of the mRNA), which is recognized by SRP. The SRP-signal peptide complex moves to the ER, where it interacts with its receptor and a nearby protein translocator. The translocator facilitates entry of the complex into the ER. The remainder of the protein enters the ER. The signal peptidase cleaves the signal peptide from the protein, thereby finalizing the protein's entry into the ER lumen. An ER-retention signal is necessary for the protein to stay within the ER after folding.
The SRP system is applicable to protein targeting to other areas, too. For example, the SRP system targets proteins to the Golgi, lysosome, plasma membrane, and secretory vesicles. However, the retention signals (if necessary) vary. Below is a chart detailing the requirements for targeting to each structure:
Two kinds of targeting exist: co-translational (during translation) and post-translational (after translation). Any SRP-associated pathway is co-translational. Targeting to the following organelles is post-translational: mitochondria, chloroplasts, peroxisomes, nucleus, and sometimes even organelles traditionally considered co-translational targets.
Here are some extra resources relating to this topic:
https://en.wikipedia.org/wiki/Target_peptide - Wikipedia page that goes in-depth into targeting.
https://www.youtube.com/watch?v=XCLfdGbySAA - explains SRP targeting to the ER.
Brooker’s Genetics - Goated genetics book.
