Sci. Signal., 4 November 2008
Microbiology The Importance of Meeting at the Pole
L. Bryan Ray
Science, Science Signaling, AAAS, Washington, DC 20005, USA
Iniesta and Shapiro report a new link in the feedback loop of signaling proteins that controls the cell division cycle of the bacterium Caulobacter crescentus. The system combines transient localization of partner proteins with phosphorylation and regulated proteolysis to ensure orderly asymmetric division of the bacterial cells. At the heart of the system is CtrA, a potent response regulator protein that directly controls transcription of about 100 genes and binds to—and thus silences—the origin of DNA replication. So, for cells to initiate DNA replication, they must inhibit activity of the phosphorylated, active form of CtrA. This happens when CtrA is degraded by the protease ClpXP, which localizes with CtrA at one end of the cell known as the pole. The localization of ClpXP requires a response regulator called CpdR, which, when unphosphorylated, localizes to the pole and activates the ClpXP protease. How does CpdR get to the pole? The new work shows that it depends on the work of another response regulator, DivK. The authors used cells lacking DivK and expression of a modified unphosphorylatable form of CpdR to show that DivK promoted dephosphorylation of CpdR and its consequent localization to the pole and degradation by ClpXP. This results in a feedback loop in which CpdR is degraded by the protease whose activation it initially supported. Then, with amounts of CpdR reduced, ClpXP is released from the pole and ceases to degrade CtrA. Bacteria thus have a complex mechanism through which all the proteins necessary to degrade CtrA are already present in the undividing cell. Then the series of localization, phosphorylation, and proteolytic steps is initiated, and the transition to cell division ensues.
A. A. Iniesta, L. Shapiro, A bacterial control circuit integrates polar localization and proteolysis of key regulatory proteins with a phospho-signaling cascade. Proc. Natl. Acad. Sci. U.S.A. 105, 16602-16607 (2008). [Abstract] [Full Text]
Citation: L. B. Ray, The Importance of Meeting at the Pole. Sci. Signal. 1, ec380 (2008).
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