Regulation of Cell-Fate Determination in Dictyostelium

Brown, Jason; Firtel, Richard A.

doi:10.1006/dbio.1999.9485

Cited by 35 publications

(21 citation statements)

References 172 publications

(191 reference statements)

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“…The biological functions of PRKX family kinases has been studied most intensively in D. discoideum, in which the PKA-C kinase has been shown to play an essential role in the cell-shape changes and cell migration necessary for cell sorting during morphogenesis as well as in the transcriptional regulation of later cell fate differentiation during development (18,19,44,45). The sole function thus far proposed for PRKX is in the regulation of granulocyte͞macrophage differentiation (11) during hematopoiesis.…”

Section: Discussionmentioning

confidence: 99%

PRKX, a phylogenetically and functionally distinct cAMP-dependent protein kinase, activates renal epithelial cell migration and morphogenesis

Amsler

et al. 2002

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

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The human protein kinase X gene (PRKX) is a member of an ancient family of cAMP-dependent serine͞threonine kinases here shown to be phylogenetically distinct from the classical PKA, PKB͞Akt, PKC, SGK, and PKG gene families. Renal expression of the PRKX gene is developmentally regulated and restricted to the ureteric bud epithelium of the fetal metanephric kidney. Aberrant adult kidney expression of PRKX was found in autosomal dominant polycystic kidney disease. PRKX kinase expression markedly activated migration of cultured renal epithelial cells in the presence of cAMP; this effect was blocked by cell treatment with the PKA inhibitor H89 and was not observed in PKA-transfected cells. In addition, expression of PRKX kinase activated branching morphogenesis of Madin-Darby canine kidney cells in collagen gels even in the absence of cAMP and͞or hepatocyte growth factor, an effect not seen with either PKA expression or expression of a mutant, kinase-inactivated PRKX. These results suggest that the PRKX kinase may regulate epithelial morphogenesis during mammalian kidney development. Because another member of the PRKX gene family (the Dictyostelium discoideum gene KAPC-DICDI) also plays a role in cellular migration, these studies suggest that regulation of morphogenesis may be a distinctive property of these genes that has been conserved in evolution that is not shared with PKA family genes.

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Section: Discussionmentioning

confidence: 99%

PRKX, a phylogenetically and functionally distinct cAMP-dependent protein kinase, activates renal epithelial cell migration and morphogenesis

Amsler

et al. 2002

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

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“…These changes involve cell chemotaxis and aggregation and differentiation into two main cell populations, the stalk cells and the spore cells. This results in the emergence of a multicellular aggregated body (the fruiting body) made up of ϳ20% dead stalk cells that support the 80% of viable spores (Soderbom and Loomis, 1998;Brown and Firtel, 1999;Thomason et al, 1999). Terminal differentiation into stalk cells has been reported to be a caspase-independent form of PCD (Cornillon et al, 1994;Olie et al, 1998), with nuclear chromatin condensation, cytoplasmic vacuolization, and the formation of a rigid cellulose cell wall.…”

Section: Discussionmentioning

confidence: 99%

“…discoideum can undergo, upon adverse environmental conditions, a complex developmental process, depending on DIF-1, cAMP secretion, and cAMP responsive gene expression, resulting in the emergence of a multicellular aggregated body (the fruiting body) made up of 20% dead stalk cells forming the stalk wall that supports the 80% viable spores (Soderbom and Loomis, 1998;Brown and Firtel, 1999;Thomason et al, 1999). Dictyostelium cells treated in the presence of DIF alone, or cAMP plus DIF, exhibit a decrease of their forward and side scatter and show a markedly decreased mitochondrial membrane potential in up to 74 and 83% of cells, respectively (Figure 6a).…”

Section: Ddaif Is Also Released During Developmental Cell Death Inducmentioning

confidence: 99%

On the Evolutionary Conservation of the Cell Death Pathway: Mitochondrial Release of an Apoptosis-inducing Factor duringDictyostelium discoideumCell Death

Arnoult

Tatischeff

Estaquier

et al. 2001

MBoC

146

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Mitochondria play a pivotal role in apoptosis in multicellular organisms by releasing apoptogenic factors such as cytochrome c that activate the caspases effector pathway, and apoptosis-inducing factor (AIF) that is involved in a caspase-independent cell death pathway. Here we report that cell death in the single-celled organism Dictyostelium discoideum involves early disruption of mitochondrial transmembrane potential (⌬⌿m) that precedes the induction of several apoptosis-like features, including exposure of the phosphatidyl residues at the external surface of the plasma membrane, an intense vacuolization, a fragmentation of DNA into large fragments, an autophagy, and the release of apoptotic corpses that are engulfed by neighboring cells. We have cloned a Dictyostelium homolog of mammalian AIF that is localized into mitochondria and is translocated from the mitochondria to the cytoplasm and the nucleus after the onset of cell death. Cytoplasmic extracts from dying Dictyostelium cells trigger the breakdown of isolated mammalian and Dictyostelium nuclei in a cell-free system, and this process is inhibited by a polyclonal antibody specific for Dictyostelium discoideum apoptosis-inducing factor (DdAIF), suggesting that DdAIF is involved in DNA degradation during Dictyostelium cell death. Our findings indicate that the cell death pathway in Dictyostelium involves mitochondria and an AIF homolog, suggesting the evolutionary conservation of at least part of the cell death pathway in unicellular and multicellular organisms. INTRODUCTIONProgrammed cell death (PCD) is a genetically regulated physiological process of cell suicide that is central to the development and homeostasis of multicellular organisms (Raff, 1992;Steller, 1995;Jacobson et al., 1997;Vaux and Korsmeyer, 1999). The basic machinery that controls the onset of PCD in roundworms (Caenorhabditis elegans), insects (Drosophila melanogaster), and vertebrates (mammals) appears to be present in all cells, at all times. Crucial aspects of PCD appear to be conserved, including both the genes encoding the basic cell death machinery, and the morphological and biochemical features of apoptosis, the most frequent phenotype of PCD (Jacobson et al., 1997;Horvitz, 1999;Song and Steller, 1999;Vaux and Korsmeyer, 1999).Mitochondria play a pivotal role in PCD in mammalian cells, in particular through the permeabilization/disruption of their outer membrane, with (or followed by) the loss of mitochondrial transmembrane potential (⌬⌿m) (Kroemer et al., 1995;Green and Reed, 1998;Petit et al., 1998;Goldstein et al., 2000;Martinou et al., 2000), leading to the release of cytochrome c (Liu et al., 1996) and apoptosis-inducing factor # Corresponding author. E-mail address: pxpetit@zeus.cochin.inserm.fr. Abbreviations used: AIF, apoptosis-inducing factor; BSA, bovine serum albumin; DIF-1, differentiation-inducing factor-1; PCR, polymerase chain reaction; ⌬⌿m, mitochondrial transmembrane potential; PCD, programmed cell death; PPIX, protoporphyrin IX; PBS, phosphate-buffered saline. ©...

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“…Despite the few cell types involved, D. discoideum development has many aspects in common with the developmental processes of more complex organisms. There are counting mechanisms that regulate the size of the structure (6), mechanisms that maintain a fixed proportion of stalk and spore cells (7,9,19), morphogenetic pathways that regulate the progression through the different developmental stages (18,25), and a coordination between stalk and spore differentiation so that spore cells differentiate only when the sporocarp is being lifted on top of the stalk (14,36).…”

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confidence: 99%

Dictyostelium discoideum Developmentally Regulated Genes Whose Expression Is Dependent on MADS Box Transcription Factor SrfA

2003

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The MADS box transcription factor SrfA is required for spore differentiation in Dictyostelium discoideum. srfA null strains form rounded spores that do not resist adverse environmental conditions. Five genes whose expression is dependent on SrfA have been isolated by differential hybridization. One of these genes, sigC, is identical to phg1b, previously characterized in mutants with altered adhesive properties and found to encode a nine-transmembrane-domain protein. This gene is transcribed into two mRNAs as the result of alternative splicing of two internal exons. The slower-migrating mRNA codes for a shorter protein that lacks the first transmembrane fragment and is not expressed in srfA null strains. The other four genes (sigA, sigB, sigD, and 45D) are expressed only during late developmental stages. In situ hybridization experiments showed that expression of sigA, sigB, and sigD is restricted to the sorus of developing structures. sigA codes for a homologue of malate dehydrogenase that converts pyruvate to malate to replenish the tricarboxylic acid cycle. sigB encodes a protein with significant similarity to the GP63 metalloproteinase of Leishmania, leishmanolysin. The sequence of SigD is highly similar to that of several spore coat proteins of D. discoideum, and it may play a role in that structure. The gene 45D codes for an RNA-binding protein homologue whose expression is also dependent on the GATA transcription factor stalky (StkA). The expression of sigB is also dependent on both SrfA and StkA. The expression of 45D, but not of sigA, sigB, sigC, and sigD, can be induced in srfA null cells by constitutive protein kinase A activation. Strains in which either sigA, sigB, or sigD is disrupted were isolated and found to form spores that are not detectably different from those of wild-type strains.

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Regulation of Cell-Fate Determination in Dictyostelium

Cited by 35 publications

References 172 publications

PRKX, a phylogenetically and functionally distinct cAMP-dependent protein kinase, activates renal epithelial cell migration and morphogenesis

PRKX, a phylogenetically and functionally distinct cAMP-dependent protein kinase, activates renal epithelial cell migration and morphogenesis

On the Evolutionary Conservation of the Cell Death Pathway: Mitochondrial Release of an Apoptosis-inducing Factor duringDictyostelium discoideumCell Death

Dictyostelium discoideum Developmentally Regulated Genes Whose Expression Is Dependent on MADS Box Transcription Factor SrfA

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