Relationships between the ligand specificity of cell surface folate binding sites, folate degrading enzymes and cellular responses in Dictyostelium discoideum

Wit, RenéJ.W. De; Bulgakov, Roman; Pinas, Johan E.; Konijn, Theo M.

doi:10.1016/0005-2736(85)90439-0

Cited by 27 publications

(14 citation statements)

References 31 publications

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“…Less than 5% degradation of 0.1 m M of all analogs was observed during 15 s incubation with a cell suspension (measured as described in Table 1). Also at 0.1 p M , less than 5% degradation of folic acid was measured within 15 s of incubation (measured as in [15]). Dose-response curves of the cellular cGMP response to various folate analogs are shown in Fig.…”

Section: Accumulation Of Cgmpmentioning

confidence: 99%

“…A more detailed study of the mechanism of action of antagonists is described in [lo]. (6) 0.17 9-Methyl folic acid (7) 0.69 10-Methyl folk acid (8) 0 Binding data are taken from [15]. Since B-and c"-sites [13,151 are two forms of the same receptor, which is now referred to as the B-receptor [9], the mean ligand specificity of B-and <?-sites is shown here.…”

Section: Accumulation Of Campmentioning

confidence: 99%

“…Recently, we described the ligand specificity of three classes of cell-surface folate-binding sites: A-, B-, and C-sites [15]. The Band C-sites seemed to be interconvertible forms of one receptor [9], which has now been designated as the B-receptor.…”

Section: Correlationsmentioning

confidence: 99%

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Developmental regulation of the pathways of folate-receptor-mediated stimulation of cAMP and cGMP synthesis in Dictyostelium discoideum

et al. 1986

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Section: Accumulation Of Cgmpmentioning

confidence: 99%

Section: Accumulation Of Campmentioning

confidence: 99%

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Developmental regulation of the pathways of folate-receptor-mediated stimulation of cAMP and cGMP synthesis in Dictyostelium discoideum

et al. 1986

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“…Thus there could either be one CMF receptor that mediates both activation of G␣ 1 as well as the G-independent activation of gene expression, or different CMF receptors with similar K D values, with one activating G␣ 1 and another activating gene expression. There is a precedent for multiple receptors sensing the same ligand in Dictyostelium; pharmacological studies indicate that there are multiple folate receptors (23,24), and four different cAMP receptors have been cloned, sequenced, and knocked out (25)(26)(27). To characterize the receptor(s) mediating cell density sensing, we used an affinity resin to purify a CMF receptor.…”

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confidence: 99%

A Putative Receptor Mediating Cell-density Sensing inDictyostelium

Deery

Gomer

1999

Journal of Biological Chemistry

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When Dictyostelium cells starve, they begin secreting a glycoprotein called conditioned medium factor (CMF). When there is a high density of starved cells, as indicated by a high concentration of CMF, the cells begin expressing some genes and aggregate using pulses of cAMP as a chemoattractant. CMF regulates gene expression via a G protein-independent pathway, whereas CMF regulates cAMP signal transduction via a G proteindependent pathway. To elucidate receptors mediating cell density sensing, we used CMF-Sepharose to isolate membrane proteins that bind CMF. We identified a 50-kDa protein, CMFR1, that is sensitive to trypsin treatment of whole cells. We obtained partial amino acid sequence of CMFR1 and isolated the cDNA encoding it. The derived amino acid sequence has no significant similarity to known proteins and has two or three predicted transmembrane domains. Expression of CMFR1 in insect cells caused an increase in CMF binding. Repression of CMFR1 in Dictyostelium by gene disruption resulted in a ϳ50% decrease of the CMF binding and a loss of CMF-induced G protein-independent gene expression. The G protein-dependent CMF signal transduction pathways appear to be functional in cmfr1 cells, suggesting that cells sense the density-sensing factor CMF using two or more different receptors.

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“…Vegetative cells have receptors for folic acid on the cell surface (3,4) while aggregating cells have receptors for cAMP (5)(6)(7). It has been thought that binding of the ligands to the receptors activates intracellular signals for activation and adaptation of guanylate cyclase.…”

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Reducing Reagent-Induced Activation of Guanylate Cyclase in the Cellular Slime Mold, Dictyostelium discoideum

Oyama

1991

The Journal of Biochemistry

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Binding of folic acid (an intrinsic agonist) to the cell surface receptors evokes transmembrane signals for activation and adaptation of guanylate cyclase in Dictyostelium discoideum. The activation signal activates this enzyme and then the adaptation signal terminates the activation. As a result, these two signals cooperatively induce a transient activation of guanylate cyclase. We investigated transmembrane signal transduction for guanylate cyclase using 2,3-dimercapto-1-propanol (BAL, a thiol-reducing reagent) since BAL induces or modifies the transmembrane signal(s). We found that BAL induced prolonged or continuous activation of guanylate cyclase. Thus, the mode of the activation is drastically different (transient versus continuous) between folic acid and BAL. We also found that the BAL-induced continuous activation was not observed when the cells were stimulated with BAL + folic acid, while folic acid + BAL transiently induced more cGMP accumulation than folic acid alone. We lastly showed that K252a, a protein kinase inhibitor, enhanced both the folic acid-induced and the BAL-induced activation of guanylate cyclase. Our results suggest that BAL induces or mimics the activation signal for guanylate cyclase. The lack of termination in the BAL-induced activation suggests that BAL does not induce the adaptation signal or that the adaptation does not inhibit the BAL-induced activation. The former possibility is more likely since folic acid suppresses the BAL-induced continuous activation. The effect of K252a suggests that protein phosphorylation plays a role in suppression of guanylate cyclase.

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Relationships between the ligand specificity of cell surface folate binding sites, folate degrading enzymes and cellular responses in Dictyostelium discoideum

Cited by 27 publications

References 31 publications

Developmental regulation of the pathways of folate-receptor-mediated stimulation of cAMP and cGMP synthesis in Dictyostelium discoideum

Developmental regulation of the pathways of folate-receptor-mediated stimulation of cAMP and cGMP synthesis in Dictyostelium discoideum

A Putative Receptor Mediating Cell-density Sensing inDictyostelium

Reducing Reagent-Induced Activation of Guanylate Cyclase in the Cellular Slime Mold, Dictyostelium discoideum

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