The Role of the Hsp40 Chaperone Sis1 in Yeast Prion Propagation

Abstract

Yeast prions are self-templating amyloid aggregates composed of misfolded cellular proteins. In order to propagate, yeast prions must be broken into heritable seeds that are passed to subsequent generations. The replication step of the prion propagation cycle is accomplished by the actions of molecular chaperones, which bind to and serve the fibers through a process called disaggregation. Prions can be thought of as molecular diseases that have hijacked the chaperones for their continued existence. When viewed in this way, the study of yeast prions has been very informative about the interactions among of the molecular chaperones. This chapter focuses on the role of a single Hsp40 or J-protein, Sis1, in the propagation of yeast prions. While Sis1 seems to be required for the maintenance of many different prions, various prions depend on Sis1 in different ways, perhaps due to differences in underlying amyloid structure. New evidence is emerging that Sis1 is important for processes that may not involve prion replication activity, providing an intriguing alternative explanation for the observed differences in the prions' reliance on Sis1.