Disruption of Dictyostelium discoideum morphogenesis by overproduction of cAMP phosphodiesterase.

Faure, Michel; Podgorski, Gregory J.; Franke, Jakob; Kessin, Richard H.

doi:10.1073/pnas.85.21.8076

Cited by 43 publications

(38 citation statements)

References 26 publications

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“…In this case, however, changes in PDE gene expression cannot be correlated with changes in cell fate because expression of the mutant regulatory subunit blocks development prior to differentiation of prestalk and prespore cells (27). Likewise, overexpression of wild-type Dictyostelium regulatory subunit by 5-to 10-fold also blocks differentiation (38), as does overexpression of secreted PDE by 30-to 100-fold (39). If more modest increases in these proteins were achieved such that cells were able to complete development, we would expect stalk cell differentiation to be favored.…”

Section: Resultsmentioning

confidence: 99%

Conditions that alter intracellular cAMP levels affect expression of the cAMP phosphodiesterase gene in Dictyostelium.

Riley¹,

Barclay²

1990

Proc. Natl. Acad. Sci. U.S.A.

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We examined expression of the Dictyostelium cAMP phosphodiesterase (PDE) gene under conditions that alter intracellular cAMP levels during in vitro differentiation of wild-type strain V12M2 and a sporogenous derivative, HB200. In control cultures, cellular PDE activity peaked at 6 hr and declined by 8 hr, while secreted PDE activity continued to increase through 8 hr. Lowering intracellular cAMP levels with caffeine or progesterone increased cellular and secreted PDE activities 2-fold, increased stalk cell differentiation, and inhibited spore differentiation. In contrast, exposure to 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP; a membrane-permeable cAMP analog) or ammonia (which promotes intracellular cAMP accumulation in V12M2 and HB200 cells) lowered PDE activities by as much as 45%, decreased stalk cell differentiation, and increased spore differentiation. Simultaneous exposure to 8-Br-cAMP and caffeine gave intermediate PDE activities as would be expected if 8-Br-cAMP entered the cell and bypassed the caffeine-mediated block to adenylate cyclase activation. In all cases, we observed commensurate changes in developmental PDE transcript levels. The developmental time course of expression was not significantly altered by these treatments. These results suggest that the magnitude of PDE gene expression is negatively regulated by intracellular cAMP levels and provide evidence for one of the earliest changes in gene expression that is consistent with cell-type specificity. These results are discussed in terms of a bistable switch employing intracellular cAMP as a regulator of cell fate. feine and progesterone, which inhibit intracellular cAMP accumulation by different mechanisms (12,13), inhibit spore and promote stalk cell differentiation in concentrationdependent manners (7). Conversely, conditions that raise intracellular cAMP levels by hyper-inducing adenylate cyclase activity increase spore and decrease stalk cell differentiation (14). Ammonia, which promotes intracellular cAMP accumulation by inhibiting its secretion (15), and 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP), a membrane-permeable cAMP analog with low affinity for the cell surface cAMP receptor (16)

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Section: Resultsmentioning

confidence: 99%

Conditions that alter intracellular cAMP levels affect expression of the cAMP phosphodiesterase gene in Dictyostelium.

Riley¹,

Barclay²

1990

Proc. Natl. Acad. Sci. U.S.A.

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“…(Barra et al, 1980;Sucgang et al, 1997). This phenotype can be rescued by the re-expression of PdsA; however, overexpression leads to aberrant development (Darmon et al, 1978;Faure et al, 1988Faure et al, , 1989. PdsA has been purified from cells and has been extensively characterized biochemically Brown and Rutherford, 1980;Blondelet and Brachet, 1981;Yamasaki and Hayashi, 1982;Franke and Kessin, 1992).…”

Section: Introductionmentioning

confidence: 99%

The Group Migration of Dictyostelium Cells Is Regulated by Extracellular Chemoattractant Degradation

Garcia

Rericha

Heger

et al. 2009

MBoC

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Starvation of Dictyostelium induces a developmental program in which cells form an aggregate that eventually differentiates into a multicellular structure. The aggregate formation is mediated by directional migration of individual cells that quickly transition to group migration in which cells align in a head-to-tail manner to form streams. Cyclic AMP acts as a chemoattractant and its production, secretion, and degradation are highly regulated. A key protein is the extracellular phosphodiesterase PdsA. In this study we examine the role and localization of PdsA during chemotaxis and streaming. We find that pdsA ؊ cells respond chemotactically to a narrower range of chemoattractant concentrations compared with wild-type (WT) cells. Moreover, unlike WT cells, pdsA ؊ cells do not form streams at low cell densities and form unusual thick and transient streams at high cell densities. We find that the intracellular pool of PdsA is localized to the endoplasmic reticulum, which may provide a compartment for storage and secretion of PdsA. Because we find that cAMP synthesis is normal in cells lacking PdsA, we conclude that signal degradation regulates the external cAMP gradient field generation and that the group migration behavior of these cells is compromised even though their signaling machinery is intact. INTRODUCTIONThe process by which cells sense an attractant molecule and respond by migrating directionally toward it is called chemotaxis. Chemotaxis is essential for a variety of physiological processes in mammals as well as for the survival of lower eukaryotes. The mechanisms that regulate the directed migration of neutrophils and Dictyostelium discoideum have been extensively studied previously (van Haastert and Devreotes, 2004;Bagorda et al., 2006;Friedl and Weigelin, 2008;Stephens et al., 2008). One particular challenge of these fast-moving cells is to maintain the ability to respond sensitively and rapidly to an attractant signal. Because both neutrophils and Dictyostelium cells use signal relay loops to propagate chemoattractant signals, mechanisms must be at play to maintain detectable levels of chemoattractants. Remarkably, signal degradation also seems to play an important role in the developmental processes of multicellular organisms. Migration of primordial germ cells in Drosophila and Zebrafish seems to require degradation of specific lysophospholipids in the former or chemokines in the latter to allow these cells to find their proper developmental environment (Renault and Lehmann, 2006;Minina et al., 2007). Many cell types use receptor-mediated degradation to maintain detectable levels of chemoattractants. In this context, cells internalize the bound receptor and as part of the receptor recycling pathway the ligand is released for degradation (Minina et al., 2007;Boldajipour et al., 2008;Borroni et al., 2008;Scola et al., 2008). Alternatively, extracellular enzymes can specifically degrade the extracellular signaling molecules, allowing the sensing machinery to go back to basal levels and retain high se...

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“…In D. discoideum, the group size is regulated in several different ways. One way is by altering the range of the aggregation territory; for instance, by altering the range of the relayed cAMP pulses that mediate aggregation (Thadani et al 1977;Faure et al 1988). …”

Section: Introductionmentioning

confidence: 99%

Two cell‐counting factors regulate the aggregate size of the cellular slime mold Dictyostelium discoideum

Okuwa¹,

Katayama²,

Takano³

et al. 2001

Dev Growth Differ

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Countin, a cell-counting factor in Dictyostelium discoideum, is considered to limit the maximum size of the multicellular structure, because a countin null strain forms a huge fruiting body compared to that of the wildtype. A novel gene, countin2, that is highly homologous to countin (40% identity in amino acid sequence) was identified in the D. discoideum genome. The countin2 null strain formed a 1.7-fold higher number of the aggregates, resulting in smaller fruiting bodies compared with those of wild-type cells. Thus, the Countin2 protein is thought to limit the minimum size of the multicellular structure. The size and number of aggregates formed by a mixture of countin null and countin2 null strains were the same as those of the wild-type. These findings demonstrate that a combination of Countin and Countin2 proteins determines the appropriate size of the multicellular structure of D. discoideum.

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Disruption of Dictyostelium discoideum morphogenesis by overproduction of cAMP phosphodiesterase.

Abstract: The development and cellular differentiation of Dictyostelium discoideum are disrupted in transformants secreting high levels of the cyclic nucleotide phosphodiesterase.

Cited by 43 publications

References 26 publications

Conditions that alter intracellular cAMP levels affect expression of the cAMP phosphodiesterase gene in Dictyostelium.

Conditions that alter intracellular cAMP levels affect expression of the cAMP phosphodiesterase gene in Dictyostelium.

The Group Migration of Dictyostelium Cells Is Regulated by Extracellular Chemoattractant Degradation

Two cell‐counting factors regulate the aggregate size of the cellular slime mold Dictyostelium discoideum

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