Regulatory interactions between phospholipid synthesis and DNA replication in Caulobacter crescentus

Abstract

Several Caulobacter crescentus mutants with lesions in phospholipid biosynthesis have DNA replication phenotypes. A C. crescentus mutant deficient in glycerol 3-phosphate dehydrogenase activity (gpsA) blocks phospholipid synthesis, ceases DNA replication, and loses viability in the absence of a glycerol phosphate supplement. To investigate the interaction between membrane synthesis and DNA replication during a single cell cycle, we moved the gpsA mutation into a synchronizable, but otherwise wild-type, strain. The first effect of withholding supplement was the cessation of synthesis of phosphatidylglycerol, a major component of the C. crescentus membrane. In the absence of glycerol 3-phosphate, DNA replication was initiated in the stalked cell at the correct time in the cell cycle and at the correct site on the chromosome. However, after replication proceeded bidirectionally for a short time, DNA synthesis dropped to a low level. The cell cycle blocked at a distinct middivision stalked cell, and this was followed by cell death. The "glycerol-less" death of the gpsA mutant could be prevented if the cells were treated with novobiocin to prevent the initiation of DNA replication. Our observations suggest that the processivity of C. crescentus replication requires concomitant phospholipid synthesis and that cell death results from incomplete replication of the chromosome.

Polar Remodeling and Histidine Kinase Activation, Which Is Essential for Caulobacter Cell Cycle Progression, Are Dependent on DNA Replication Initiation

“…Novobiocin has been shown to inhibit the initiation of DNA replication in Caulobacter (33). To determine the effect of novobiocin on the polar localization of CckA, we isolated swarmer cells from strain AA841 that contained CckA-CFP and MipZ-YFP (to label the parS/ParB/MipZ complex) and incubated these cells in the presence or absence of novobiocin (100 g/ml) for 90 min.…”

Selective cell cycle transcription requires membrane synthesis in Caulobacter

“…To analyze how cell cycle events depend on membrane synthesis, synchronous gpsA swarmer cells were isolated, washed free of the glycerol and glycerol‐3‐phoshate (GG) supplement and released into duplicate cultures either with (+GG) or without (−GG) supplement (Figure 2A). The +GG cells behave indistinguishably from the wild‐type cells, but membrane synthesis stops abruptly in the −GG cells (Loewy et al ., 1990). Although they differentiate into stalked cells (Contreras et al ., 1980; O'Neill and Bender, 1989) and initiate DNA synthesis, these −GG cells fail to complete DNA replication and they arrest uniformly as non‐motile but elongated stalked cells (Loewy et al ., 1990).…”

“…This treatment has significant consequences for the C.crescentus cell cycle (Figure 2A). For example, cell division and the initiation of a second round of chromosome replication both require phospholipid synthesis (O'Neill and Bender, 1989; Loewy et al ., 1990).…”

Participación del sistema nervioso y del tracto gastrointestinal en la homeostasis energética

“…La estimulación de las neuronas correspondientes produce reflejos viscerales que a través del núcleo del tracto solitario (NTS) de la médula espinal 112 , regulan tanto funciones gastrointestinales como la sensación de hambre y homeostasis energética. Además, este núcleo también recibe información de circuitos paralelos que provienen del sistema cardiovascular, pulmonar, respiratorio y sensorial 113 . Desde el NTS, la información se disemina a regiones del cerebro incluyendo el hipotálamo 114 produciendo un sistema complejo de señales promovidas por el apetito, la saciedad, la acomodación y secreción gástrica y motilidad 62 .…”