While prions themselves have been studied for decades, researchers are still learning how normal cellular machinery influences whether infection takes hold and how it spreads.
This study from the MRC Prion Unit at UCL, focuses on syntaxin-6 (gene STX6), a protein that helps route cargo through the cell’s internal transport system. Human genetic studies have suggested that higher STX6 expression may increase the risk of sporadic prion disease, but its functional role had not been tested directly.
Using several prion-infected cell models, the researchers found that changing syntaxin-6 levels alters prion behaviour. Reducing syntaxin-6 caused disease-related prion protein to accumulate around the cell and changed its appearance, consistent with altered intracellular trafficking. Importantly, syntaxin-6 knockdown reduced the amount of infectious prion material released from infected cells, while overexpression had the opposite overall pattern, supporting a role for syntaxin-6 in prion export.
Elizabeth Hill, a PhD student in Simon Mead’s lab, then tested whether this matters in living animals. In mice, deleting Stx6 made animals less susceptible to developing prion disease after inoculation with low prion doses, reducing the proportion that went on to become ill (“attack rate”). However, once disease was established under standard experimental conditions, syntaxin-6 did not measurably change the life span of mice, symptom onset, or markers of prion propagation and toxicity, suggesting its main effect is at an early stage of infection.
Overall, the findings support syntaxin-6 as a host “modifier”, that helps impact how prion diseases develop by influencing how materials move around inside the cell and how infectious proteins spread. The export of infectious material, highlighting cellular transport pathways as potential targets to explore in future therapeutic research.