PSF and CMF, autocrine factors that regulate gene expression during growth and early development ofDictyostelium

Clarke, Margaret; Gomer, Richard H.

doi:10.1007/bf01944730

Cited by 101 publications

(71 citation statements)

References 62 publications

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“…1 Â 10 5 cells´mL 21 ) than cells grown in bacterial suspension (. 5 Â 10 5 cells´mL 21 ) [15]. This clearly correlates with our findings that diphosphoinositol phosphates accumulate earlier during growth of cells in axenic culture than in bacterial suspension.…”

Section: R E S U L T S a N D Discussionsupporting

confidence: 89%

“…These conditions typically lead to the initiation of the prestarvation response of the cell population that is observed when the cells exceed a certain density relative to their bacterial food supply [15]. This response is accompanied by the expression of early developmental proteins, for example discoidin-I or lysosomal a-mannosidase.…”

Section: R E S U L T S a N D Discussionmentioning

confidence: 99%

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Diphospho‐myo‐inositol phosphates during the life cycle of Dictyostelium and Polysphondylium

Laussmann

Pikzack

Thiel

et al. 2000

European Journal of Biochemistry

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The intracellular amounts of diphospho-myo-inositol phosphates and InsP 6 were determined in Dictyostelium discoideum AX2 throughout the life cycle, including exponential growth, starvation, differentiation, sporulation and spore germination. Similar experiments were performed with the closely related species Polysphondylium pallidum under conditions resulting in microcyst formation. A distinct accumulation of these compounds is observed during the early starvation phase of the cell population before the onset of the actual differentiation program. When exponentially growing D. discoideum cells were shifted to starvation conditions, a 25-fold accumulation of 5,6-bis-PP-InsP 4 within 3 h was observed. In P. pallidum, the 5,6-bis-PP-InsP 4 pool rises around 20-fold within 8 h during the formation of microcysts from vegetative cells. Finally, the diphosphoinositol phosphates are deposited in spores or microcysts and are degraded when spores or microcysts germinate at low cell density.Keywords: myo-inositol; diphospho-myo-inositol phosphates; Dictyostelium; Polysphondylium.Cellular slime molds like Dictyostelium and Polysphondylium are ancient amoebae that are able to form multicellular aggregates when their food supply is exhausted. The cells of these aggregates differentiate in spore and stalk cells and finally form fruiting bodies. Alternatively, some species can form microcysts as a resistant stage when exposed to increased osmolarity. Under suitable conditions, spores or microcysts can germinate and release solitary living amoebae [1].Diphosphoinositol phosphates were originally discovered in the Dictyostelium discoideum wild-type strain NC4 [2]. In that study, an inositol phosphate derivative was observed that eluted after InsP 6 from an anion-exchange column. It was tentatively suggested that this compound, called`InsP y ', is a`pyrophosphate form of InsP 6 ' [3]. Meanwhile, InsP y from the genus Dictyostelium has been analyzed by HPLC and NMR and was found to consist of three different diphosphoinositol phosphates, namely 5-PP-InsP 5 , 6-PP-InsP 5 , and 5,6-bis-PP-InsP 4 . 5-PP-InsP 5 and 6-PP-InsP 5 can not be completely separated by anion-exchange HPLC but can be distinguished enzymatically using a kinase that specifically phosphorylates 6-PP-InsP 5 but not 5-PP-InsP 5 in isolated PP-InsP 5 fractions. In the closely related genus Polysphondylium, an additional compound of this type has been detected and identified as 1,5-bis-PP-InsP 4 or its enantiomer 3,5-bis-PP-InsP 4 [4,5].The metabolism of highly phosphorylated inositol phosphates during the development of Dictyostelium has been investigated in a previous study by monitoring the incorporation of [ 3 H]inositol into these compounds [3]. It was found that InsP 6 incorporates [ 3 H]inositol continuously for 8 h after onset of starvation. In contrast, no incorporation into InsP y , which corresponds to the sum of diphosphoinositol phosphates, could be seen during the first 3 h of starvation. After this lag phase, InsP y was linearly labeled by [ 3 H]inosit...

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Section: R E S U L T S a N D Discussionsupporting

confidence: 89%

Section: R E S U L T S a N D Discussionmentioning

confidence: 99%

Diphospho‐myo‐inositol phosphates during the life cycle of Dictyostelium and Polysphondylium

Laussmann

Pikzack

Thiel

et al. 2000

European Journal of Biochemistry

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“…Similar calculations showed that when many cells in a region starve, the extracellular CMF concentration could reach 0.3 ng/ml after 2 h of secretion. Interestingly, for aggregates of fewer than roughly 45 cells, the CMF concentration can never rise to 0.3 ng/ml, indicating that CMF could be used to sense whether there are more than 45 cells in an aggregate [19]. The solutions are not unique: many combinations of secretion rate, diffusion coefficient, and threshold sensitivity will allow density sensing.…”

Section: Introductionmentioning

confidence: 99%

A cell‐density sensing factor regulates the lifetime of a chemoattractant‐induced Gα‐GTP conformation

1997

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Starving Dictyostelium discoideum cells monitor the local density of other starving cells by simultaneously secreting and sensing CMF. CMF regulates signal transduction through the chemoattractant cAMP receptor, cARl. cARl activates a heterotrimeric G protein by stimulating Goc2 to release GDP and bind GTP. We show here that the rate of cAMP-stimulated GTP hydrolysis in membranes from cells exposed to CMF is roughly 4 times slower than in membranes from untreated cells, even though the rate of GTP binding is the same. This hydrolysis is abolished in cells lacking Goc2. Our data thus suggest that CMF regulates cAMP signal transduction in part by prolonging the lifetime of the Ga2-GTP complex.

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“…Disruption of countin, a gene encoding one of the subunits of CF, resulted in cells that formed large fruiting bodies due to streams staying intact and coalescing into large groups (22). Diffusion calculations based on the observed accumulation rate of CF indicated that in general the concentration of a secreted factor such as CF could be used to indicate to cells the number of cells in a stream or group (22,23).…”

mentioning

confidence: 99%

Disruption of Aldehyde Reductase Increases Group Size in Dictyostelium

Ehrenman

Gong

Hong

et al. 2004

Journal of Biological Chemistry

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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.

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PSF and CMF, autocrine factors that regulate gene expression during growth and early development ofDictyostelium

Cited by 101 publications

References 62 publications

Diphospho‐myo‐inositol phosphates during the life cycle of Dictyostelium and Polysphondylium

Diphospho‐myo‐inositol phosphates during the life cycle of Dictyostelium and Polysphondylium

A cell‐density sensing factor regulates the lifetime of a chemoattractant‐induced Gα‐GTP conformation

Disruption of Aldehyde Reductase Increases Group Size in Dictyostelium

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