December 04, 2017
Barney Stinson from the sitcom “How I Met Your Mother” is right—the accidental curly fry in your plate of fries is a wonderful thing. It is unexpected but adds immensely to the French fry eating experience.
In a new study in GENETICS, Hoffmann and coworkers show that spore wall lipid droplets, organelles used to move neutral lipids to the cell wall in the yeast Saccharomyces cerevisiae, have a surprise component, too. Instead of an errant curly fry in an order of fries, the greasy droplet has long chain polyisoprenoids made by Srt1p and its partner, Nus1p.
And in an unexpected twist, they are not used to glycosylate a protein as most polyprenols do. No, they upregulate the activity of a key protein involved in spore wall synthesis—Chs3p. Polyprenols may have more varied roles than scientists thought. A pleasant surprise indeed.
Yeast need many factors to make these resistant walls. One is Chs3p, the chitin synthase that makes the chitin that is used to make one of the four spore cell wall layers. Another is the lipid droplet that brings a variety of lipids and proteins to the site of the expanding cell wall.
Hoffmann and coworkers used transmission electron microscopy (TEM) to show that spores from strains deleted for SRT1 lack the chitosan layer of their cell walls. Additional experiments showed that this strain is missing this layer because it fails to make chitin as opposed to failing to be able to assemble chitin properly.
The Srt1p/Nus1p complex is a cis–prenyltransferase—it adds 5-carbon isopentyl groups to farnesyl diphosphate to make polyprenols. In the next set of experiments, these researchers showed that an enzymatically inactive mutant of Srt1p, Srt1p-D75A, did not make the chitosan layer as well. This suggested that it is the long chain polyisoprenoids that Srt1p/Nus1p synthesizes that matters for spore wall formation.
In the final set of experiments, Hoffmann and coworkers showed that extracts lacking Srt1p had decreased chitin synthase activity. In other words, they showed that the activity of Chs3p is dependent on Srt1p.
Taken together, these results suggest that polyprenols like long chain polyisoprenoids may do more than simply facilitate the glycosylation of proteins. Here, they upregulate the activity of a protein involved in cell wall synthesis.
And we aren’t just talking yeast either. Most every living thing, including people, have polyprenol-derived dolichols which carry sugars to facilitate protein glycosylation. It may be that these types of molecules also have hidden, unexpected roles. Researchers may want to give these molecules a second look to see if they missed that extra curly fry.
Taking a man’s bonus curly is inexcusable.
by Barry Starr, Ph.D., Director of Outreach Activities, Stanford Genetics
Categories: Research Spotlight