The Protein Quality Control Network in Caulobacter crescentus

Abstract

The asymmetric life cycle of Caulobacter crescentus has provided a model in which to study how protein quality control (PQC) networks interface with cell cycle and developmental processes, and how the functions of these systems change during exposure to stress. As in most bacteria, the PQC network of Caulobacter contains highly conserved ATP-dependent chaperones and proteases as well as more specialized holdases. During growth in optimal conditions, these systems support a regulated circuit of protein synthesis and degradation that drives cell differentiation and cell cycle progression. When stress conditions threaten the proteome, most components of the Caulobacter proteostasis network are upregulated and switch to survival functions that prevent, revert, and remove protein damage, while simultaneously pausing the cell cycle in order to regain protein homeostasis. The specialized physiology of Caulobacter influences how it copes with proteotoxic stress, such as in the global management of damaged proteins during recovery as well as in cell type-specific stress responses. Our mini-review highlights the discoveries that have been made in how Caulobacter utilizes its PQC network for regulating its life cycle under optimal and proteotoxic stress conditions, and discusses open research questions in this model.

Integrative visualization of the molecular structure of a cellular microdomain

“…The AAA+ protease ClpXP degrades CtrA in a cell cycle‐dependent manner (Fatima et al, 2022 ; Joshi & Chien, 2016 ; Schroeder & Jonas, 2021 ). CpdR, RcdA, and the cdG receptor PopA are required for degradation of CtrA by ClpXP when bound to the chromosome.…”

The Lon protease temporally restricts polar cell differentiation events during the Caulobacter cell cycle

“…Previous work established that the ClpP protease with its unfoldases ClpA and ClpX has key roles in C. crescentus development by mediating the temporally and spatially controlled degradation of several important cell cycle regulators ( Joshi and Chien, 2016 ; Schroeder and Jonas, 2021 ). In addition to ClpXP, Lon plays an important role in C. crescentus cell cycle regulation ( Joshi and Chien, 2016 ; Schroeder and Jonas, 2021 ).…”

“…Previous work established that the ClpP protease with its unfoldases ClpA and ClpX has key roles in C. crescentus development by mediating the temporally and spatially controlled degradation of several important cell cycle regulators ( Joshi and Chien, 2016 ; Schroeder and Jonas, 2021 ). In addition to ClpXP, Lon plays an important role in C. crescentus cell cycle regulation ( Joshi and Chien, 2016 ; Schroeder and Jonas, 2021 ). It degrades the swarmer cell-specific transcription factor SciP ( Gora et al, 2013 ), the methyltransferase and transcriptional regulator CcrM ( Wright et al, 1996 ), and the conserved replication initiator DnaA ( Jonas et al, 2013 ).…”

Discovering Genetic Modulators of the Protein Homeostasis System through Multilevel Analysis

“…Still, most proteostasis network components, like chaperones and proteases, are conserved during billion years of evolution (4). Notably, research on Caulobacter crescentus underscores the dynamic roles of these networks in regulating both the cell cycle and stress responses (5).…”