Aggregation of proteins due to failure of quality control mechanisms is deleterious to both eukaryotes and prokaryotes. We found that in Escherichia coli, protein aggregates are delivered to the pole and form a large polar aggregate (LPA). The formation of LPAs involves two steps: the formation of multiple small aggregates and the delivery of these aggregates to the pole to form an LPA. Formation of randomly distributed aggregates, their delivery to the poles, and LPA formation are all energy-dependent processes. The latter steps require the proton motive force, activities of the DnaK and DnaJ chaperones, and MreB. About 90 min after their formation, the LPAs are dissolved in a process that is dependent upon ClpB, DnaK, and energy. Our results confirm and substantiate the notion that the formation of LPAs allows asymmetric inheritance of the aggregated proteins to a small number of daughter cells, enabling their rapid elimination from most of the bacterial population. Moreover, the results show that the processing of aggregated proteins by the protein quality control system is a multi-step process with distinct spatial and temporal controls.
Bibliographical noteFunding Information:
This work was supported by grants from the National Institutes of Health (R21 AI071240-01 to Amos Oppenheim and Marcia Goldberg), the Israel–United States Bi-National Foundation, and the Israel Science Foundation, which was founded by the Israel Academy of Science and Humanities. I.R. is an Etta Rosensohn Professor of Bacteriology. We thank Ariella Oppenheim for her support and insightful comments. We thank Nathalie Balaban and Sivan Pearl for their help with microscopy.
- polar localization
- protein aggregation
- protein quality control