Peptide signaling during terminal differentiation of<i>Dictyostelium</i>

Anjard, Christophe; Loomis, William F.

doi:10.1073/pnas.0501820102

Cited by 88 publications

(147 citation statements)

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“…Encapsulated spores were recognized as phase bright by phase-contrast microscopy (7,8). The proportion of encapsulated cells rose from 14% to 35% by 90 min, which is the same timing and level of spore formation observed upon addition of SDF-1 and is significantly slower and less efficient than what is observed upon addition of SDF-2 or cytokinins (2,3,7,8). Moreover, the induction of spore differentiation by MPBD, like induction by SDF-1, could be blocked by simultaneous addition of cycloheximide to inhibit protein synthesis (Fig.…”

Section: Resultsmentioning

confidence: 68%

“…Synthetic SDF-1 (phosphokemptide) and SDF-2 have been previously described (3,4). SDF-1 and SDF-2 produced by cells were purified as previously reported (1,3).…”

Section: Methodsmentioning

confidence: 99%

“…The protease that processes AcbA into SDF-2 is fused to an ABC transporter embedded in the membrane and encoded by the prestalk-specific gene tagC (3,8). Antibodies raised against the TagC protease domain block processing of recombinant AcbA to SDF-2 when added to whole cells following treatment with GABA (3, 4).…”

Section: Vol 10 2011 Signaling Cascade In Dictyostelium 959mentioning

confidence: 99%

“…One of these is the 34-amino-acid peptide SDF-2, which is proteolytically generated from acyl-coenzyme A (CoA) binding protein (AcbA) following secretion in response to GABA (3,4). SDF-2 binds to the receptor histidine kinase DhkA, leading to the accumulation of cAMP and the activation of PKA (43).…”

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confidence: 99%

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The Polyketide MPBD Initiates the SDF-1 Signaling Cascade That Coordinates Terminal Differentiation in Dictyostelium

Anjard

Loomis

2011

Eukaryot Cell

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Dictyostelium uses a wide array of chemical signals to coordinate differentiation as it switches from a unicellular to a multicellular organism. MPBD, the product of the polyketide synthase encoded by stlA, regulates stalk and spore differentiation by rapidly stimulating the release of the phosphopeptide SDF-1. By analyzing specific mutants affected in MPBD or SDF-1 production, we delineated a signal transduction cascade through the membrane receptor CrlA coupled to G␣1, leading to the inhibition of GskA so that the precursor of SDF-1 is released. It is then processed by the extracellular protease of TagB on prestalk cells. SDF-1 apparently acts through the adenylyl cyclase ACG to activate the cyclic AMP (cAMP)-dependent protein kinase A (PKA) and trigger the production of more SDF-1. This signaling cascade shows similarities to the SDF-2 signaling pathway, which acts later to induce rapid spore encapsulation.

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Section: Resultsmentioning

confidence: 68%

“…Synthetic SDF-1 (phosphokemptide) and SDF-2 have been previously described (3,4). SDF-1 and SDF-2 produced by cells were purified as previously reported (1,3).…”

Section: Methodsmentioning

confidence: 99%

Section: Vol 10 2011 Signaling Cascade In Dictyostelium 959mentioning

confidence: 99%

mentioning

confidence: 99%

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The Polyketide MPBD Initiates the SDF-1 Signaling Cascade That Coordinates Terminal Differentiation in Dictyostelium

Anjard

Loomis

2011

Eukaryot Cell

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“…sgkB is a sphingosine kinase gene that we have already described as having a role in cisplatin resistance (14), and we now find that three other genes (acbA, atg8, and smlA) also had altered cisplatin sensitivity. Interestingly, acbA encodes an acylCoA binding protein, which is involved in sphingolipid metabolism and in developmental intercellular signaling, including the regulation of long-chain base sphingolipid by the yeast homolog Acb1p (34,(42)(43)(44). atg8 participates in the regulation of autophagy, a process in which cells use internal organelles and macromolecules as a source of nutrients and energy and in which conjugation to phosphatidylethanolamine plays a key role (35,45,46).…”

Section: Discussionmentioning

confidence: 99%

Global transcriptional responses to cisplatin in Dictyostelium discoideum identify potential drug targets

Driessche¹,

Alexander

Kuspa

et al. 2007

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

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Dictyostelium discoideum is a useful model for studying mechanisms of cisplatin drug sensitivity. Our previous findings, that mutations in sphingolipid metabolism genes confer cisplatin resistance in D. discoideum and in human cells, raised interest in the resistance mechanisms and their implications for cisplatin chemotherapy. Here we used expression microarrays to monitor physiological changes and to identify pathways that are affected by cisplatin treatment of D. discoideum. We found >400 genes whose regulation was altered by cisplatin treatment of wild-type cells, including groups of genes that participate in cell proliferation and in nucleotide and protein metabolism, showing that the cisplatin response is orderly and multifaceted. Transcriptional profiling of two isogenic cisplatin-resistant mutants, impaired in different sphingolipid metabolism steps, showed that the effect of cisplatin treatment was greater than the effect of the mutations, indicating that cisplatin resistance in the mutants is due to specific abilities to overcome the drug effects rather than to general drug insensitivity. Nevertheless, the mutants exhibited significantly different responses to cisplatin compared with the parent, and >200 genes accounted for that difference. Mutations in five cisplatin response genes (sgkB, csbA, acbA, smlA, and atg8) resulted in altered drug sensitivity, implicating novel pathways in cisplatin response. Our data illustrate how modeling complex cellular responses to drugs in genetically stable and tractable systems can uncover new targets with the potential for improving chemotherapy.drug resistance ͉ sphingolipids ͉ sphingosine kinase ͉ sphingosine-1-phosphate lyase ͉ transcriptional profiling D ictyostelium discoideum is well known for studies of cell and developmental biology and is gaining interest as a model for studying human disease, including cancer (1). A substantial body of work has accumulated using D. discoideum to identify genes and proteins associated with resistance to the anti-cancer drug cisplatin (2).Cisplatin [cis-diamminedichloroplatinum(II)] is used to treat a variety of solid tumors (3), but efficacy is often limited by drug resistance (4). Studies in human tumor cells and cell lines have implicated a number of resistance mechanisms and demonstrated that resistance is multifaceted (5).D. discoideum provides a genetically tractable system to the problem of cisplatin resistance. It is a eukaryote with cellular properties similar to those of human cells (6). Its genome is sequenced, and many genes are homologous to human genes (7). Using insertional mutagenesis screens (8), we isolated mutants with single gene disruptions that have decreased sensitivity to cisplatin (9). One of these strains was null for the sphingosine-1-phosphate (S-1-P) lyase gene sglA, establishing the first link between sphingolipid metabolism and cisplatin sensitivity and defining S-1-P lyase as a potential target for controlling cisplatin sensitivity.S-1-P synthesis is catalyzed by sphingosine kinase from sphin...

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Evolution of size and pattern in the social amoebas

Schaap

2007

BioEssays

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A fundamental goal of biology is to understand how novel phenotypes evolved through changes in existing genes. The Dictyostelia or social amoebas represent a simple form of multicellularity, where starving cells aggregate to build fruiting structures. This review summarizes efforts to provide a framework for investigating the genetic changes that generated novel morphologies in the Dictyostelia. The foundation is a recently constructed molecular phylogeny of the Dictyostelia, which was used to examine trends in the evolution of novel forms and in the divergence of genes that shape these forms. There is a major trend towards the formation of large unbranched fruiting bodies, which is correlated with the use of cyclic AMP (cAMP) as a secreted signal to coordinate cell aggregation. The role of cAMP in aggregation arose through co-option of a pathway that originally acted to coordinate fruiting body formation. The genotypic changes that caused this innovation and the role of dynamic cAMP signaling in defining fruiting body size and pattern throughout social amoeba evolution are discussed. BioEssays 29:635–644, 2007. © 2007 Wiley Periodicals, Inc.

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Peptide signaling during terminal differentiation ofDictyostelium

Cited by 88 publications

References 35 publications

The Polyketide MPBD Initiates the SDF-1 Signaling Cascade That Coordinates Terminal Differentiation in Dictyostelium

The Polyketide MPBD Initiates the SDF-1 Signaling Cascade That Coordinates Terminal Differentiation in Dictyostelium

Global transcriptional responses to cisplatin in Dictyostelium discoideum identify potential drug targets

Evolution of size and pattern in the social amoebas

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