Temporal and spatial regulation of CtrA proteolysis

            The transcription factor CtrA is required for Caulobacter viability, regulating cell division, DNA methylation, and the synthesis of polar structures such as the flagellum, stalk, and pili. However, CtrA also binds to sites within the chromosomal origin of replication and inhibits the initiation of DNA replication. To reconcile these opposing activities, CtrA is present and active at some stages of the cell cycle, but is rapidly proteolyzed just before chromosome replication begin


            In the cell, regulated CtrA proteolysis requires the protease ClpXP and three accessory proteins (CpdR, RcdA, and PopA). All of these proteins converge at one pole of the cell during CtrA degradation. The timing of CtrA proteolysis is controlled in part by modulating the activity of the accessory proteins. For example, CpdR is only active in its unphosphorylated form, and it becomes dephosphorylated during swarmer-to-stalked cell development. Additionally, PopA is only active when bound to the small signaling molecule cyclic diguanylate (cdG), and there is an increase in cdG concentration during swarmer cell development.

            We seem to have a lot of information about CtrA proteolysis, but significant mysteries remain. First, although the accessory proteins are needed for CtrA degradation in vivo, CtrA can be proteolyzed by purified ClpXP alone in vitro. So what do the accessory proteins actually do? Second, how are the protease, accessory factors, and substrate targeted to the cell pole at the time of CtrA proteolysis? We know that proteins within this complex depend on each other for localization, but we do not know what protein(s) act as a landing pad at the cell pole.