title: Heat shock transcription factor σ32 co-opts the signal recognition particle to regulate protein homeostasis in E. coli.
abstract: All cells must adapt to rapidly changing conditions. The heat shock response (HSR) is an intracellular signaling pathway that maintains proteostasis (protein folding homeostasis), a process critical for survival in all organisms exposed to heat stress or other conditions that alter the folding of the proteome. Yet despite decades of study, the circuitry described for responding to altered protein status in the best-studied bacterium, E. coli, does not faithfully recapitulate the range of cellular responses in response to this stress. Here, we report the discovery of the missing link. Surprisingly, we found that σ(32), the central transcription factor driving the HSR, must be localized to the membrane rather than dispersed in the cytoplasm as previously assumed. Genetic analyses indicate that σ(32) localization results from a protein targeting reaction facilitated by the signal recognition particle (SRP) and its receptor (SR), which together comprise a conserved protein targeting machine and mediate the cotranslational targeting of inner membrane proteins to the membrane. SRP interacts with σ(32) directly and transports it to the inner membrane. Our results show that σ(32) must be membrane-associated to be properly regulated in response to the protein folding status in the cell, explaining how the HSR integrates information from both the cytoplasm and bacterial cell membrane.
authors.affiliation: Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, California, United States of America.
authors.forename: Bentley
authors.initials: B
authors.lastname: Lim
authors.affiliation: Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Miyazaki
authors.affiliation: Department of Biochemistry and Biophysics and Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, California United States of America.
authors.forename: Saskia
authors.initials: S
authors.lastname: Neher
authors.affiliation: Department of Biology, Texas A&M University, College Station, Texas, United States of America.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Siegele
authors.affiliation: Faculty of Life Sciences, Kyoto Sangyo University, Kyoto, Japan.
authors.forename: Koreaki
authors.initials: K
authors.lastname: Ito
authors.affiliation: Department of Biochemistry and Biophysics and Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, California United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Walter
authors.affiliation: Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Akiyama
authors.affiliation: Faculty of Life Sciences, Kyoto Sangyo University, Kyoto, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yura
authors.affiliation: Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, California, United States of America ; Department of Cell and Tissue Biology, University of California at San Francisco, San Francisco, California, United States.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Gross
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000502:physiology; D004926:Escherichia coli / Q000502:physiology; D029968:Escherichia coli Proteins / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D017510:Protein Folding; D012808:Sigma Factor / Q000502:physiology*; D018271:Signal Recognition Particle / Q000502:physiology*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; D012808:Sigma Factor; D018271:Signal Recognition Particle; C069774:heat-shock sigma factor 32