Everything old is new again: An update on current research on the Cpx envelope stress response

• Published in: Biochimica et biophysica acta Vol. 1843; no. 8; pp. 1529 - 1541
• Main Author: Raivio, Tracy L.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2014
• Subjects: Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Escherichia coli - genetics; Escherichia coli - metabolism; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - metabolism; Gene Expression Regulation, Bacterial; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; Membrane Proteins - metabolism; Periplasm - genetics; Periplasm - metabolism; Post-transcriptional regulation; Protein Folding; Protein Kinases - chemistry; Protein Kinases - metabolism; RNA Processing, Post-Transcriptional - genetics; Signal Transduction - genetics; Two-component signal transduction; Two-component signal transduction; Post-transcriptional regulation
• ISSN: 0167-4889; 0006-3002; 1879-2596
• DOI: 10.1016/j.bbamcr.2013.10.018

The Cpx envelope stress response (ESR) has been linked to proteins that are integrated into and secreted across the inner membrane for several decades. Initial studies of the cpx locus linked it to alterations in the protein content of both the inner and outer membrane, together with changes in proton motive driven transport and conjugation. Since the mid 1990s, the predominant view of the Cpx envelope stress response has been that it serves to detect and respond to secreted, misfolded proteins in the periplasm. Recent studies in Escherichia coli and other Gram negative organisms highlight a role for the Cpx ESR in specifically responding to perturbations that occur at the inner membrane (IM). It is clear that Cpx adaptation involves a broad suite of changes that encompass many functions in addition to protein folding. Interestingly, recent studies have refocused attention on Cpx-regulated phenotypes that were initially published over 30years ago, including antibiotic resistance and transport across the IM. In this review I will focus on the insights and models that have arisen from recent studies and that may help explain some of the originally published Cpx phenotypes. Although the molecular nature of the inducing signal for the Cpx ESR remains enigmatic, recently solved structures of signaling proteins are yielding testable models concerning the molecular mechanisms behind signaling. The identification of connections between the Cpx ESR and other stress responses in the cell reveals a complex web of interactions that involves Cpx-regulated expression of other regulators as well as small proteins and sRNAs. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey. •The CpxAR pathway mediates adaptation to envelope stresses at the inner membrane.•Cpx adaptation is multi‐faceted, affecting energy generation and transport.•Many Cpx inducers known; they enter the pathway at multiple points.•Cpx response connects to other pathways through regulation of regulators and sRNAs.•Cpx pathway regulated by other signaling pathways, sRNAs, small regulatory 18 molecules.