The cell density factor CMF regulates the chemoattractant receptor cAR1 in Dictyostelium.

Haastert, Peter J.M. van; Bishop, John D.; Gomer, Richard H.

doi:10.1083/jcb.134.6.1543

Cited by 35 publications

(31 citation statements)

References 35 publications

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“…Although there are about 4 ϫ 10 4 receptors on Dictyostelium cells for the glycoprotein cell density-sensing factor CMF and an equal number of receptors for the chemoattractant cAMP (45)(46)(47), there appear to be only ϳ53 receptors for countin (18) and ϳ56 receptors for CF50. Similarly low numbers of receptors have been observed in many other systems (18).…”

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

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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.

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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

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“…Vegetative cells have little CMF binding and few cAMP receptors, whereas starved cells possess about 40,000 receptors for CMF and cAMP. Transformants overexpressing cAR1 show a 10-fold increase of cAMP binding and a similar increase of CMF binding; disruption of the cAR1 gene abolishes both cAMP and CMF binding (22). In wild-type cells, high levels of cAMP down-regulate both cAMP and CMF binding, and CMF similarly down-regulates both cAMP and CMF binding.…”

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confidence: 98%

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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“…Binding of roughly 200 molecules of CMF to starved cells affects the affinity of the majority of the 40 000 cARls within 2 min, indicating that the linkage involves an amplifying mechanism. In cells lacking G|3, cAMP induces a loss of cAMP binding but not CMF binding, while CMF induces a reduction of CMF binding without affecting cAMP binding, suggesting that the linkage between the CMF and cAMP signal transduction pathways is through a G protein [22]. Cells lacking CMF have normal levels of cARl, cAMP-induced binding of GTP or GTP-yS to membranes, and GTPyS modulatable cAMP binding, suggesting that the interaction of the cAMP receptor with G proteins in vitro is not measurably affected by CMF.…”

Section: Introductionmentioning

confidence: 99%

“…The activations of Ca 2+ influx, adenylyl cyclase, and guanylyl cyclase in response to a pulse of cAMP are strongly inhibited in cells lacking CMF, but are restored by a 10 s exposure of the cells to CMF. Down-regulation of cARl with high levels of cAMP also down-regulates CMF binding [21], and CMF similarly downregulates cAMP and CMF binding, indicating a linkage between the two signal transduction systems [22]. Binding of roughly 200 molecules of CMF to starved cells affects the affinity of the majority of the 40 000 cARls within 2 min, indicating that the linkage involves an amplifying mechanism.…”

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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The cell density factor CMF regulates the chemoattractant receptor cAR1 in Dictyostelium.

Cited by 35 publications

References 35 publications

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

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

A Putative Receptor Mediating Cell-density Sensing inDictyostelium

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

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