J. Cell Biol. doi:10.1083/jcb.200911115 (2010)

Many proteins carry signal sequences — segments that act like shipping labels, directing the protein to specific structures in the cell. Ramanujan Hegde at the National Institute of Child Health and Human Development in Bethesda, Maryland, and his colleagues looked at the efficiency of the signal sequence on the mammalian prion protein (PrP), which can cause neurodegenerative disease when misfolded or mutated.

They found that roughly 10% of PrP made by cells is misdirected, which is consistent with previous work. The authors engineered disease-causing versions of mutant PrP with signal sequences that more efficiently guide the protein to its destination. Mice producing the modified proteins were protected against neurodegeneration.

The work highlights a potential contributory factor to prion diseases.