Making saliva is quite a complex business

There’s more to saliva than meets the eye – and mouth. Researchers in the US and Norway have taken a close look at where the multitude of proteins floating in the fluid come from, and found it’s a complicated story.

There are three major types of human salivary glands, individual cells within a single gland can secrete different proteins, it seems, and there are even proteins in the mouth that appear to be coming from elsewhere, such as epithelial tissues or blood plasma.

At the same time, some proteins that help regulate gene expression are predominantly active in salivary glands, but not in other tissues.

“Before this, scientists had an idea of the proteins that are found in the mouth, but we didn’t have a complete picture of where they were coming from. We’re addressing this gap,” says Omer Gokcumen from the University at Buffalo, US, co-author of the team’s paper in the journal Cell Reports.

To unravel the story, the researchers first sought to understand which proteins are produced by each major type of salivary gland: the parotid, submandibular and sublingual glands (humans have a pair of each).

They used transcriptomics (the study of RNA molecules in a cell) to measure gene activity in each kind of gland. Gene activity provides insight into protein production, because each gene provides instructions for making a specific protein.

From this they were able to understand the proteins that each gland generates, and how the glands differ from one another in terms of what they produce.

For instance, they report, the parotid and submandibular glands create a lot of salivary amylase, an enzyme that helps to digest starch, while the sublingual gland makes almost none. It does, however, produce relatively large quantities of certain GalNAc transferases, a family of enzymes that’s important in initiating a process called O-glycosylation that attaches a sugar to certain salivary mucin proteins.

“Our work reveals that even a gland type itself is not homogenous,” says Sarah Knox from the University of California, San Francisco. “The saliva-producing acinar cells, which were once thought to produce the same proteins, and thus be the same cells, actually synthesise distinct saliva proteins, thus indicating a new level of cellular diversity.”

From a biomedical perspective, the research opens the door for further studies into the functions of saliva and salivary glands, and the use of saliva as a diagnostic fluid, says Buffalo’s Stefan Ruhl.

“Our study takes a snapshot of how healthy salivary glands should function. Deviations from this healthy expectation can indicate disease.”