Cellular quality control of protein aggregates

Abstract

The aggregation of misfolded proteins in cells is controlled by chaperones including the small Hsp, Hsp70 and Hsp100. We have investigated the spatio‐temporal features of the aggregation of fluorescently labeled thermolabile proteins in heat‐treated bacteria and yeast cells. In bacteria, aggregates are almost exclusively deposited at the poles; upon cell division the old pole is the preferred site of aggregation. Membrane associated thermolabile proteins form aggregates along the longitudinal axis of the cell, and can serve as seed to relocalise aggregation‐prone proteins of the cytosol to the membrane. Upon heat treatment major components of the chaperone machinery of the cell almost completely relocalise to the aggregates. This occurs in a hierarchical fashion with distinct kinetics for each chaperone. Moreover, the relocalisation of some chaperones is prerequisite for the relocalisation of others. Mechanistic details of the disaggregation process by the ClpB/DnaK bi‐chaperone system will be provided. In yeast, the aggregation of thermolabile proteins initially occurs at multiple locations. During recovery typically 1‐2 prominent deposits are remaining, reminiscent of those identified recently by J. Frydman et al. We identified a role for some chaperones in the formation of these aggregates, indicating that chaperones are implicated in the cellular compartmentalisation of aggregates.