Traffic delays might do more than make you late to work. Findings from Kim et al. now suggest that slowed trafficking of the γ-secretase protease might cause Alzheimer's disease.
γ-Secretase is a multisubunit complex that includes presenilin. Mutations in presenilin are associated with inherited forms of Alzheimer's. Scientists do not yet understand how these varied mutations—which can fall at multiple points along the protein—all lead to the misprocessing of the amyloid precursor protein to create an aggregation-prone form of Aβ.
Presenilin is assembled with the rest of the γ-secretase complex within the secretory pathway. In the new report, the team found that trafficking through at least part of this pathway—out of the ER and into COPII vesicles—was slowed by presenilin mutations that cause Alzheimer's. Packaging of the mutants into COPII vesicles was reduced in in vitro ER budding assays.
Exit from the ER is often...
