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PNAS 101 (19): 7415-7420

Copyright © 2004 by the National Academy of Sciences.


Recruitment of a cytoplasmic response regulator to the cell pole is linked to its cell cycle-regulated proteolysis

Kathleen R. Ryan *, Sarah Huntwork, and Lucy Shapiro {dagger}

Department of Developmental Biology, Beckman Center for Molecular and Genetic Medicine, Stanford University School of Medicine, Stanford, CA 94305

Contributed by Lucy Shapiro, March 29, 2004

Abstract: The response regulator CtrA, which silences the Caulobacter origin of replication and controls multiple cell cycle events, is specifically proteolyzed in cells preparing to initiate DNA replication. At the swarmer-to-stalked cell transition and in the stalked compartment of the predivisional cell, CtrA is localized to the cell pole just before its degradation. Analysis of the requirements for CtrA polar localization and CtrA proteolysis revealed that both processes require a motif within amino acids 1-56 of the CtrA receiver domain, and neither process requires CtrA phosphorylation. These results strongly suggest that CtrA polar localization is coupled to its cell cycle-regulated proteolysis. The polarly localized DivK response regulator promotes CtrA localization and proteolysis, but it does not directly recruit CtrA to the cell pole. Mutations in the divJ and pleC histidine kinases perturb the characteristic asymmetry of CtrA localization and proteolysis in the predivisional cell. We propose that polar recruitment of CtrA evolved to ensure that CtrA is degraded only in the stalked half of the predivisional cell, perhaps by localizing a proteolytic adaptor protein to the stalked pole. This is an example of controlled proteolysis of a cytoplasmic protein that is associated with its active recruitment to a specific subcellular address.

Key Words: Caulobacter • CtrA • ClpXP

Abbreviations: SW-ST, swarmer-to-stalked cell; YFP, yellow fluorescent protein; FACS, fluorescence-activated cell sorter; DIC, differential interference contrast.

* Present address: Department of Plant and Microbial Biology, 371 Koshland Hall, University of California, Berkeley, CA 94720.

{dagger} To whom correspondence should be addressed. E-mail: shapiro{at}

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