cAMP‐dependent protein kinase activity is essential for preaggregative gene expression in <i>Dictyostelium</i>

Schulkes, Conchita C.G.M.; Schaap, Pauline

doi:10.1016/0014-5793(95)00676-z

Cited by 63 publications

(52 citation statements)

References 29 publications

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“…These defects are probably due to the defect in the activation of cAMP and signal relay, as rip3 null cells induce all three classes of genes in response to exogenous cAMP. PKA activity is required for multiple developmental pathways, including aggregation (Mann and Firtel, 1991;Reymond et al, 1995;Schulkes and Schaap, 1995;Mann et al, 1997). We demonstrate that constitutive expression of the PKA catalytic subunit does not complement the rip3 null phenotype, indicating that rip3 null cells have sufficient levels of endogenous PKA activity for these processes.…”

Section: Discussionmentioning

confidence: 84%

A Novel Ras-interacting Protein Required for Chemotaxis and Cyclic Adenosine Monophosphate Signal Relay inDictyostelium

Lee

Parent

Insall

et al. 1999

MBoC

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We have identified a novel Ras-interacting protein from Dictyostelium, RIP3, whose function is required for both chemotaxis and the synthesis and relay of the cyclic AMP (cAMP) chemoattractant signal. rip3 null cells are unable to aggregate and lack receptor activation of adenylyl cyclase but are able, in response to cAMP, to induce aggregation-stage, postaggregative, and cell-type-specific gene expression in suspension culture. In addition, rip3 null cells are unable to properly polarize in a cAMP gradient and chemotaxis is highly impaired. We demonstrate that cAMP stimulation of guanylyl cyclase, which is required for chemotaxis, is reduced ϳ60% in rip3 null cells. This reduced activation of guanylyl cyclase may account, in part, for the defect in chemotaxis. When cells are pulsed with cAMP for 5 h to mimic the endogenous cAMP oscillations that occur in wild-type strains, the cells will form aggregates, most of which, however, arrest at the mound stage. Unlike the response seen in wild-type strains, the rip3 null cell aggregates that form under these experimental conditions are very small, which is probably due to the rip3 null cell chemotaxis defect. Many of the phenotypes of the rip3 null cell, including the inability to activate adenylyl cyclase in response to cAMP and defects in chemotaxis, are very similar to those of strains carrying a disruption of the gene encoding the putative Ras exchange factor AleA. We demonstrate that aleA null cells also exhibit a defect in cAMP-mediated activation of guanylyl cyclase similar to that of rip3 null cells. A double-knockout mutant (rip3/aleA null cells) exhibits a further reduction in receptor activation of guanylyl cyclase, and these cells display almost no cell polarization or movement in cAMP gradients. As RIP3 preferentially interacts with an activated form of the Dictyostelium Ras protein RasG, which itself is important for cell movement, we propose that RIP3 and AleA are components of a Ras-regulated pathway involved in integrating chemotaxis and signal relay pathways that are essential for aggregation.

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Section: Discussionmentioning

confidence: 84%

A Novel Ras-interacting Protein Required for Chemotaxis and Cyclic Adenosine Monophosphate Signal Relay inDictyostelium

Lee

Parent

Insall

et al. 1999

MBoC

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“…Similarly there was considerable inhibition in the level of expression of another early developmental gene, pde. Early developmental gene expression has also been shown to be repressed in mutants which are deficient in the synthesis of cAMP (15,18,30,38), and when pVEII-rasG-G12T cells were pulsed with cAMP for 4 h, car1 and pde expression was restored to wild-type levels. In addition, cells were capable of aggregating and forming fruiting bodies after being pulsed with cAMP in suspension.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of an Activated rasG Gene during Growth Blocks the Initiation of Dictyostelium Development

Khosla

Spiegelman

Weeks

1996

Molecular and Cellular Biology

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Transformants that expressed either the wild-type rasG gene, an activated rasG-G12T gene, or a dominant negative rasG-S17N gene, all under the control of the folate-repressible discoidin (dis1␥) promoter, were isolated. All three transformants expressed high levels of Ras protein which were reduced by growth in the presence of folate. All three transformants grew slowly, and the reduction in growth rate correlated with the amount of RasG protein produced, suggesting that RasG is important in regulating cell growth. The pVEIIrasG transformant containing the wild-type rasG gene developed normally despite the presence of high levels of RasG throughout development. This result indicates that the down regulation of rasG that normally occurs during aggregation of wild-type strains is not essential for the differentiation process. Dictyostelium transformants expressing the dominant negative rasG-S17N gene also differentiated normally. Dictyostelium transformants that overexpressed the activated rasG-G12T gene did not aggregate. The defect occurred very early in development, since the expression of car1 and pde, genes that are normally induced soon after the initiation of development, was repressed. However, when the transformant cells were pulsed with cyclic AMP, expression of both genes returned to wild-type levels. The transformants exhibited chemotaxis to cyclic AMP, and development was synergized by mixing with wild-type cells. Furthermore, cells that were pulsed with cyclic AMP for 4 h before being induced to differentiate by plating on filters produced small, but otherwise normal, fruiting bodies. These results suggest that the rasG-G12T transformants are defective in cyclic AMP production and that RasG ⅐ GTP blocks development by interfering with the initial generation of cyclic AMP pulses.

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“…When the ratio of PSF relative to that of bacteria exceeds a certain threshold, cells stop proliferating and initiate the expression of genes that are required for their aggregation (Clarke and Gomer, 1995). Early on during aggregation, gene expression requires the activity of cAMP-dependent protein kinase (PKA) (Schulkes and Schaap, 1995), and a high PSF to food ratio is thought to upregulate the translation of the PKA catalytic subunit PKA-C (Souza et al, 1999;Souza et al, 1998).…”

Section: From Unicellular Amoeba To Fruiting Bodymentioning

confidence: 99%

Evolutionary crossroads in developmental biology: Dictyostelium discoideum

Schaap

2011

Development

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SummaryDictyostelium discoideum belongs to a group of multicellular life forms that can also exist for long periods as single cells. This ability to shift between uni-and multicellularity makes the group ideal for studying the genetic changes that occurred at the crossroads between uni-and multicellular life. In this Primer, I discuss the mechanisms that control multicellular development in Dictyostelium discoideum and reconstruct how some of these mechanisms evolved from a stress response in the unicellular ancestor.Key words: Evolution of multicellularity, Social amoeba, Encystation, Sporulation, Dictyostelium IntroductionThe social amoebas, or Dictyostelia, are a group of organisms that become multicellular by aggregation and then proceed to build fruiting bodies that consist of stalk cells and spores (see Glossary, Box 1). This developmental cycle is a response to starvation, and involves both highly coordinated cell movement and a tightly controlled programme of cell differentiation. Social amoebas belong to the supergroup of Amoebozoa (see Glossary, Box 1), a sister group to the clade of Opisthokonts (see Glossary, Box 1), which contains the animals and fungi. All supergroups contain unicellular protist-like organisms (see Glossary, Box 1) and, in several groups, multicellular life forms have evolved independently (Minge et al., 2009).The Amoebozoa supergroup consists mainly of unicellular amoeba-like organisms that have a simple life cycle. The feeding amoeba or trophozoite turns into a dormant cyst when faced with food shortage, drought or other life-threatening circumstances (Cavalier-Smith et al., 2004). Several clades of Amoebozoa have given rise to protostelid-like organisms (see Glossary, Box 1), which form a very simple fruiting body (see Glossary, Box 1) that consists of a single spore that sits on a simple stalk made by the same cell (Shadwick et al., 2009). However, only the Dictyostelia are able to form multicellular fruiting bodies that contain up to a million cells (Fig. 1).There are ~120 known species of Dictyostelia and a molecular phylogeny has been constructed to reveal the order in which they evolved (Schaap et al., 2006). The phylogeny subdivides species into four major groups (Fig. 2), with the model social amoeba Dictyostelium discoideum belonging to the most recently diverged group 4. Many species in groups 1-3 can still encyst as single cells when conditions are unfavourable for aggregation. However, group 4 species have lost the ability to encyst. Strikingly, all group 4 species tested secrete cyclic adenosine monophosphate (cAMP) to act as a chemoattractant for aggregation. This is most unusual, because almost all other organisms only use cAMP inside the cell to transduce the effect of other secreted stimuli, such as hormones, mating factors and neurotransmitters. None of the species in groups 1-3 uses cAMP for aggregation; some use glorin, a modified dipeptide of glutamate and ornithine, whereas others use folic acid, pterin or other as yet unidentified chemoattractants (Schaap e...

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cAMP‐dependent protein kinase activity is essential for preaggregative gene expression in Dictyostelium

Cited by 63 publications

References 29 publications

A Novel Ras-interacting Protein Required for Chemotaxis and Cyclic Adenosine Monophosphate Signal Relay inDictyostelium

A Novel Ras-interacting Protein Required for Chemotaxis and Cyclic Adenosine Monophosphate Signal Relay inDictyostelium

Overexpression of an Activated rasG Gene during Growth Blocks the Initiation of Dictyostelium Development

Evolutionary crossroads in developmental biology: Dictyostelium discoideum

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