title: Anionic lipids and the cytoskeletal proteins MreB and RodZ define the spatio-temporal distribution and function of membrane stress controller PspA in Escherichia coli.
abstract: All cell types must maintain the integrity of their membranes. The conserved bacterial membrane-associated protein PspA is a major effector acting upon extracytoplasmic stress and is implicated in protection of the inner membrane of pathogens, formation of biofilms and multi-drug-resistant persister cells. PspA and its homologues in Gram-positive bacteria and archaea protect the cell envelope whilst also supporting thylakoid biogenesis in cyanobacteria and higher plants. In enterobacteria, PspA is a dual function protein negatively regulating the Psp system in the absence of stress and acting as an effector of membrane integrity upon stress. We show that in Escherichia coli the low-order oligomeric PspA regulatory complex associates with cardiolipin-rich, curved polar inner membrane regions. There, cardiolipin and the flotillin 1 homologue YqiK support the PspBC sensors in transducing a membrane stress signal to the PspA-PspF inhibitory complex. After stress perception, PspA high-order oligomeric effector complexes initially assemble in polar membrane regions. Subsequently, the discrete spatial distribution and dynamics of PspA effector(s) in lateral membrane regions depend on the actin homologue MreB and the peptidoglycan machinery protein RodZ. The consequences of loss of cytoplasmic membrane anionic lipids, MreB, RodZ and/or YqiK suggest that the mode of action of the PspA effector is closely associated with cell envelope organization.
authors.affiliation: Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
authors.forename: Goran
authors.initials: G
authors.lastname: Jovanovic
authors.affiliation: Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
authors.forename: Parul
authors.initials: P
authors.lastname: Mehta
authors.affiliation: National Heart and Lung Institute, Imperial College London, London SW7 2AZ, UK.
authors.forename: Liming
authors.initials: L
authors.lastname: Ying
authors.affiliation: Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Buck
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D021381:Protein Transport; D013312:Stress, Physiological
chemical_list: D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; D008055:Lipids; C538795:RodZ protein, E coli; C069816:phage shock protein, Bacteria; C078473:MreB protein, E coli