Achieving proper polarity is essential for cellular function. In bacteria, cell polarity has been observed by using both morphological and molecular markers; however, no general regulators of bacterial cell polarity have been identified. Here we investigate the effect on cell polarity of two cytoskeletal elements previously implicated in cell shape determination. We find that the actin-like MreB protein mediates global cell polarity in Caulobacter crescentus, although the intermediate filament-like CreS protein influences cell shape without affecting cell polarity. MreB is organized in an axial spiral that is dynamically rearranged during the cell cycle, and MreB dynamics may be critical for the determination of cell polarity. By examining depletion and overexpression strains, we demonstrate that MreB is required both for the polar localization of the chromosomal origin sequence and the dynamic localization of regulatory proteins to the correct cell pole. We propose that the molecular polarity inherent in an actin-like filament is translated into a mechanism for directing global cell polarity.T he bacterium Caulobacter crescentus is particularly well suited to studies of cell polarity because of its inherently asymmetric life cycle that yields, at each cell division, progeny that have different polar morphologies and cell fates (Fig. 1C). The larger ''stalked'' cell progeny has a cytoplasmic extension known as a stalk at one pole, and the smaller ''swarmer'' cell progeny has a flagellum and pili at one pole. Immediately after cell division, the stalked cell initiates DNA replication, grows, and synthesizes a flagellum and a pilus secretion apparatus at the pole opposite the stalk before dividing asymmetrically (1). After emerging from a brief G1 arrest, the swarmer cell sheds its flagellum and pili, develops a stalk at that same pole, and initiates DNA replication. This new stalked cell then proceeds through the same asymmetric life cycle as other stalked cells. The stalk is clearly identifiable by light microscopy, making it easy to monitor Caulobacter polarity throughout the cell cycle. In addition, several structural and regulatory proteins as well as the origin of replication have been shown to dynamically localize to the stalked pole, the swarmer pole, or both poles during the cell cycle (2). These proteins and chromosomal regions serve as molecular markers of cell polarity. Subcellularly localized molecules are not unique to Caulobacter. For example, chemoreceptors, histidine kinases, response regulators, and several chromosomal loci have specific addresses in a wide variety of bacteria, including those without obvious morphological asymmetry (3-7). In addition, virtually every eukaryotic cell has subcellularly localized proteins, such as secretory molecules localized to the bud tip in yeast and neurotransmitter receptors localized to neuronal synapses (8, 9).The mechanism by which Caulobacter cells achieve such exquisite polarity is unknown, and no global regulators of cell polarity have been identified i...