Cell cycle control by oscillating regulatory proteins in Caulobacter crescentus

Abstract

Significant strides have been made in recent years towards understanding the molecular basis of cell cycle progression in the model bacterium Caulobacter crescentus. At the heart of cell cycle regulation is a multicomponent transcriptional feedback loop, governing the production of successive regulatory waves or pulses of at least three master regulatory proteins. These oscillating master regulators direct the execution of phase-specific events and, importantly, through intrinsic genetic switches not only determine the length of a given phase, but also provide the driving force that catapults the cell into the next stage of the cell cycle. The genetic switches act as fail safe mechanisms that prevent the cell cycle from relapsing and thus govern the ordered production and the periodicity of these regulatory waves. Here, we detail how the master regulators CtrA, GcrA and DnaA coordinate cell cycle progression and polar development in Caulobacter.

Polar Localization of the CckA Histidine Kinase and Cell Cycle Periodicity of the Essential Master Regulator CtrA in Caulobacter crescentus

“…2A and B). Because the length of the cell cycle varies among growing cells (even within the same agarose-padded slide), it remained unclear if delocalization preceded or followed cytokinesis (i.e., the cytoplasmic compartmentalization of the predivisional cell), a key cell cycle event that determines the fate of daughter cells (2,5,7,16,20,42). Cytokinesis triggers many changes in the cell, including the release of DivK from the new pole into the swarmer cell compartment, while DivK remains localized at the old pole in the stalked cell compartment (27,37).…”

“…The alphaproteobacterium Caulobacter crescentus provides a model system that has been particularly useful for unraveling the bacterial cell cycle (2,5,7,16,20,42). Its life cycle is characterized by an asymmetric cell division that yields two distinct daughter cells, the motile swarmer cell and the sessile stalked cell.…”

Transcription network and cyclin/CDKs: The yin and yang of cell cycle oscillators

“…In addition, they regulate each other's transcription to create a cell cycle oscillator (reviewed in ref. 28).…”

Phenotypic Variation and Bistable Switching in Bacteria

“…Asynchronously growing cells can display different phenotypes depending on the stage of the cell cycle or the growth. Cell cycle-related variation plays an important role in the coordinate expression of genes required for replication and cell division (Holtzendorff et al 2006;Avery 2006), and has been shown to be responsible for the heterogeneous expression of certain proteins (Sumner and Avery 2002;Rosenfeld et al 2005). Biological cycles also occur on a longer time scale, as in circadian rhythms (Williams 2007).…”

“…In addition, a combination of a positive and a negative interaction is capable of inducing rhythmic oscillations. This type of regulation is a key component of both cell cycle regulation and circadian rhythms (Holtzendorff et al 2006;Williams 2007). Finally, it was shown that a three-component negative feedback loop (repressilator) can also cause oscillatory behavior (Elowitz and Leibler 2000).…”