Prions Ex Vivo: What Cell Culture Models Tell Us about Infectious Proteins
Figure 2
Mitotic stability of aggregate phenotypes is indicative of aggregate fragmentation. Dividing cells are a good model system to study propagation propensities of protein aggregates. (a) Proteins that can propagate as prions are mitotically stable in tissue culture, meaning that they are bidirectionally transmitted to daughter cells. Generation of infectious seeds that can self-propagate must be at least as fast as cell division. Prion aggregates must also be capable of escaping effective cellular clearance mechanisms. PrPSc, NM derived prions [57, 58], and some SOD1 mutants [59] fulfill these criteria. (b) Many protein aggregates are mitotically instable. Unidirectional segregation during cell division might represent an evolutionary conserved mechanism to protect a subset of the progeny cells from toxic effects of protein aggregates. Relatively poor mitotic stability has been reported for polyQ aggregates [60, 61].
