We are looking at modifying the signal peptide of a receptor in a common immortalized human cell line. The cell line already expresses an unusually high amount of the protein, but much of it is not surface expressed.
When we compared the sequence of the signal peptide in the cell line (in this specific case the first 19AA), we found 2 mutations vs the wild type (WT) sequence. One obvious idea, which we will do, is to restore the peptide to the WT version.
But I've been curious about options that increase trafficking to the plasma membrane over WT. When I've looked up groups that have actually done this, it's normally been with large screens against every possible mutation in the signal peptide.
Are there targeted approaches to choosing a small number of signal peptides to increase surface expression?
I'm playing around with swapping it out some viral peptides that are totally unrelated to see if we can get increased expression with a receptor that's still (semi) functional.