A Secreted Cell Number Counting Factor Represses Intracellular Glucose Levels to Regulate Group Size in Dictyostelium

Jang, Wonhee; Chiem, Binh; Gomer, Richard H.

doi:10.1074/jbc.m205635200

Cited by 24 publications

(71 citation statements)

References 41 publications

(56 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As shown in Fig. 12, the level of glucose in the vegetative (0 h of starvation) and 6-h starved wild-type cells was similar to what we previously observed for Ax4 cells (35) and somewhat lower than what we previously observed for 2-h starved cells. Compared with the parental cells, the alrA Ϫ cells had lower glucose levels, with a statistically significant difference at 4 h. These results indicate that disruption of alrA causes cells to contain lower rather than higher levels of glucose.…”

Section: Disrupting Aldehyde Reductase Results In Hugementioning

confidence: 38%

“…We previously found that CF represses cytosolic glucose levels and that increasing cytosolic glucose levels increases group size (35). This suggested that glucose or some metabolite of glucose might affect group size.…”

Section: Discussionmentioning

confidence: 99%

“…High levels of glucose cause cells to form large fruiting bodies (34). CF appears to decrease intracellular glucose levels (35). Increasing glucose levels by adding exogenous glucose negates the effect of CF on group size and mimics the effect of decreasing CF on the cAMP-stimulated cAMP pulse, adhesion, and motility.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Disruption of Aldehyde Reductase Increases Group Size in Dictyostelium

Ehrenman

Gong

Hong

et al. 2004

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Developing Dictyostelium cells form structures containing ϳ20,000 cells. The size regulation mechanism involves a secreted counting factor (CF) repressing cytosolic glucose levels. Glucose or a glucose metabolite affects cell-cell adhesion and motility; these in turn affect whether a group stays together, loses cells, or even breaks up. NADPH-coupled aldehyde reductase reduces a wide variety of aldehydes to the corresponding alcohols, including converting glucose to sorbitol. The levels of this enzyme previously appeared to be regulated by CF. We find that disrupting alrA, the gene encoding aldehyde reductase, results in the loss of alrA mRNA and AlrA protein and a decrease in the ability of cell lysates to reduce both glyceraldehyde and glucose in an NADPH-coupled reaction. Counterintuitively, alrA ؊ cells are responsive to CF and are partially responsive to recombinant countin and CF50, suggesting that disrupting alrA inhibits but does not completely block the CF signal transduction pathway. Gas chromatography/mass spectroscopy indicates that the concentrations of several metabolites are altered in alrA ؊ cells, suggesting that the Dictyostelium aldehyde reductase affects several metabolic pathways in addition to converting glucose to sorbitol. Together, our data suggest that disrupting alrA affects CF secretion, causes many effects on cellular metabolism, and has a major effect on group size.

show abstract

Section: Disrupting Aldehyde Reductase Results In Hugementioning

confidence: 38%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Disruption of Aldehyde Reductase Increases Group Size in Dictyostelium

Ehrenman

Gong

Hong

et al. 2004

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Exogenous glucose increases the cAMP-stimulated cAMP pulse, whereas altering the size of the external cAMP pulse with cAMP phosphodiesterase or exogenous cAMP pulses does not affect glucose levels, suggesting that glucose lies upstream of the cAMP pulses in the CF signal transduction pathway (44). This suggests that countin and CF50 have the same effect on glucose, and the effect of recombinant CF50 on the cAMP pulse size is by a pathway that appears to bypass the effect of CF50 on glucose levels.…”

Section: Discussionmentioning

confidence: 62%

“…Disrupting either countin or cf50 increases glucose levels in cells, and exogenous glucose negates the effects of either recombinant countin or recombinant CF50 on group size (17,44). Exogenous glucose increases the cAMP-stimulated cAMP pulse, whereas altering the size of the external cAMP pulse with cAMP phosphodiesterase or exogenous cAMP pulses does not affect glucose levels, suggesting that glucose lies upstream of the cAMP pulses in the CF signal transduction pathway (44).…”

Section: Discussionmentioning

confidence: 99%

Two Components of a Secreted Cell Number-counting Factor Bind to Cells and Have Opposing Effects on cAMP Signal Transduction in Dictyostelium

Brock

Ehrenman

Ammann

et al. 2003

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

A secreted 450-kDa complex of proteins called counting factor (CF) is part of a negative feedback loop that regulates the size of the groups formed by developing Dictyostelium cells. Two components of CF are countin and CF50. Both recombinant countin and recombinant CF50 decrease group size in Dictyostelium. countin ؊ cells have a decreased cAMP-stimulated cAMP pulse, whereas recombinant countin potentiates the cAMP pulse. We find that cf50؊ cells have an increased cAMP pulse, whereas recombinant CF50 decreases the cAMP pulse, suggesting that countin and CF50 have opposite effects on cAMP signal transduction. In addition, countin and CF50 have opposite effects on cAMP-stimulated Erk2 activation. However, like recombinant countin, recombinant CF50 increases cell motility. We previously found that cells bind recombinant countin with a Hill coefficient of ϳ2, a K H of 60 pM, and ϳ53 sites/cell. We find here that cells also bind 125 I-recombinant CF50, with a Hill coefficient of ϳ2, a K H of ϳ15 ng/ml (490 pM), and ϳ56 sites/cell. Countin and CF50 require each other's presence to affect group size, but the presence of countin is not necessary for CF50 to bind to cells, and CF50 is not necessary for countin to bind to cells. Our working hypothesis is that a signal transduction pathway activated by countin binding to cells modulates a signal transduction pathway activated by CF50 binding to cells and vice versa and that these two pathways can be distinguished by their effects on cAMP signal transduction.

show abstract

Polyamines regulate cell growth and cellular methylglyoxal in high‐glucose medium independently of intracellular glutathione

et al. 2016

View full text Add to dashboard Cite

Edited by Miguel De la RosaPolyamines can presumably inhibit protein glycation, when associated with the methylglyoxal inevitably produced during glycolysis. Herein, we hypothesized a nonenzymatic interaction between putrescine and methylglyoxal in putrescine-deficient or -overexpressing Dictyostelium cells in high-glucose medium, which can control methylglyoxal production. Putrescine was essentially required for growth rescue accompanying methylglyoxal detoxification when cells underwent growth defect and cell cycle G1-arrest when supplemented with high glucose. Furthermore, methylglyoxal regulation by putrescine seemed to be a parallel pathway independent of the changes in cellular glutathione content in high-glucose medium. Consequently, we suggest that Dictyostelium cells need polyamines for normal growth and cellular methylglyoxal regulation.Keywords: Dictyostelium discoideum; glutathione; methylglyoxal; polyamines; putrescine High amounts of cellular glucose, a simple aldosic monosaccharide and a reducing sugar, can cause cellular damage that is followed by increased production of chemically reactive MG in mammals [1]. Glucose has been elucidated as a major a-dicarbonyl compound causing AGEs to form and furthermore is associated with engagement of their cellular RAGE in diabetic complications [2]. Particularly, MG has been strongly suggested to activate nonenzymatic glycation of proteins to form irreversible AGEs [3,4]. Although the biochemical origins of MG production have still not been addressed distinctly [5], MG seems to alter the intracellular content of both GSH and ROS in eukaryotes [6].To explain the biochemical roles of MG and its regulating enzymes, many types of enzyme systems have been proposed in mammals [7,8]. In microorganisms, our current study revealed that cellular MG levels altered Candida cell physiology and differentiation through their MG-consuming enzyme systems [9,10]. Additionally, we previously reported the crucial effect of MG on cell growth, cell cycle, and differentiation when MG-reducing aldose reductase (AlrA) is regulated in Dictyostelium [11]. However, nonenzymatic MG-scavenging molecules have not been sufficiently studied either in vitro or in vivo. The limited cellular MG regulation by MG-consuming enzymes is not sufficient for the nonenzymatic MG production,

show abstract

A Secreted Cell Number Counting Factor Represses Intracellular Glucose Levels to Regulate Group Size in Dictyostelium

Cited by 24 publications

References 41 publications

Disruption of Aldehyde Reductase Increases Group Size in Dictyostelium

Disruption of Aldehyde Reductase Increases Group Size in Dictyostelium

Two Components of a Secreted Cell Number-counting Factor Bind to Cells and Have Opposing Effects on cAMP Signal Transduction in Dictyostelium

Polyamines regulate cell growth and cellular methylglyoxal in high‐glucose medium independently of intracellular glutathione

Contact Info

Product

Resources

About