Genome-Wide Expression Analyses of Gene Regulation during Early Development of
            <i>Dictyostelium discoideum</i>

Iranfar, Negin; Fuller, Danny; Loomis, William F.

doi:10.1128/ec.2.4.664-670.2003

Cited by 86 publications

(92 citation statements)

References 42 publications

(62 reference statements)

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“…cAR1 and G␣2, initially expressed at low levels, maximally induce their own expression and that of other pulse-induced genes by triggering the elevation of intracellular cAMP and activation of PKA (Iranfar et al, 2003). cAR1 controls intracellular cAMP levels through the simultaneous activation of ACA and ERK2-mediated inhibition of the cAMP-specific PDE RegA (Maeda et al, 2004), which are both subject to adaptation.…”

Section: Discussionmentioning

confidence: 99%

Constitutively Active G Protein-coupled Receptor Mutants BlockDictyosteliumDevelopment

Zhang¹,

Goswami²,

Hereld³

2005

MBoC

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cAR1, a G protein-coupled receptor (GPCR) for cAMP, is required for the multicellular development of Dictyostelium. The activation of multiple pathways by cAR1 is transient because of poorly defined adaptation mechanisms. To investigate this, we used a genetic screen for impaired development to isolate four dominant-negative cAR1 mutants, designated DN1-4. The mutant receptors inhibit multiple cAR1-mediated responses known to undergo adaptation. Reduced in vitro adenylyl cyclase activation by GTP␥S suggests that they cause constitutive adaptation of this and perhaps other pathways. In addition, the DN mutants are constitutively phosphorylated, which normally requires cAMP binding and possess cAMP affinities that are ϳ100-fold higher than that of wild-type cAR1. Two independent activating mutations, L100H and I104N, were identified. These residues occupy adjacent positions near the cytoplasmic end of the receptor's third transmembrane helix and correspond to the (E/D)RY motif of numerous mammalian GPCRs, which is believed to regulate their activation. Taken together, these findings suggest that the DN mutants are constitutively activated and block development by turning on natural adaptation mechanisms. INTRODUCTIONG protein-coupled receptors (GPCRs) number in the thousands in humans and are responsible for physiological responses to diverse extracellular signals including light, odorants, hormones, chemoattractants, and neurotransmitters. On activation by their ligands (or photons in the case of rhodopsin), these seven transmembrane domain-containing receptors typically activate heterotrimeric G proteins that, in turn, regulate the activities of a variety of downstream effectors. Ligand binding also triggers various desensitization mechanisms which diminish the cell's responsiveness to subsequent stimulation (Strader et al., 1995;Bourne, 1997;Ferguson and Caron, 1998).These systems are highly conserved and found in all eukaryotes including the social amoeba Dictyostelium discoideum, which uses extracellular cAMP signaling and cAMPspecific GPCRs to orchestrate its multicellular development. When deprived of nutrients, this free-living soil amoeba ceases growth and embarks on a 24-h program in which some 10 5 cells aggregate and differentiate to yield a sporeladen fruiting body. The first of four highly homologous cAMP receptors (cARs) expressed during development, cAR1, is essential for aggregation and subsequent development for three principal reasons. First, by transiently activating an adenylyl cyclase (ACA), cAR1 mediates "cAMP relay," the amplification and propagation of cAMP waves, which arise spontaneously every 6 min at aggregation centers. Second, cAR1 plays a direct role in aggregation as it mediates chemotaxis of cells up the cAMP gradient inherent in each oncoming wave. Lastly, cAR1 is responsible for the induction of various aggregation-stage genes including those encoding cAR1 itself, ACA, and G␣2, the G protein ␣-subunit through which cAR1 signals (Parent and Devreotes, 1996). cAR1 governs these di...

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Section: Discussionmentioning

confidence: 99%

Constitutively Active G Protein-coupled Receptor Mutants BlockDictyosteliumDevelopment

Zhang¹,

Goswami²,

Hereld³

2005

MBoC

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“…Dictyostelium cells exhibit a dramatic gene expression pattern shift after starvation, and necessary "early genes" start to express during early development (14). Thus we examined the expression profiles of early genes including cAR1 and csA in grlB Ϫ cells.…”

Section: A Gaba B Receptor-like Protein Grlb Is Involved In Earlymentioning

confidence: 99%

“…This organism also produces GABA in both vegetative and developmental stages (13). Two genes encoding GAD, gadA and gadB, have been identified in the D. discoideum genome (14). These two proteins share high protein sequence identity (73%) but display a distinct temporal expression pattern, suggesting they function non-redundantly in growth and development.…”

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confidence: 99%

“…These two proteins share high protein sequence identity (73%) but display a distinct temporal expression pattern, suggesting they function non-redundantly in growth and development. Microarray analysis showed that the gadA mRNA expression dramatically increases at 10 h after development and peaks at 18 h during the culmination stage (15), whereas gadB mRNA is expressed in vegetative cells and diminishes after the onset of starvation (14). Only one GABA transaminase gene, gabT, was identified in the D. discoideum genome (16).…”

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confidence: 99%

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Systematic Analysis of γ-Aminobutyric Acid (GABA) Metabolism and Function in the Social Amoeba Dictyostelium discoideum

Janetopoulos

2013

Journal of Biological Chemistry

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Background: GABA promotes terminal differentiation during late development of Dictyostelium discoideum. Results: GABA metabolism is tightly controlled and regulates early development. Conclusion: Distinct genes regulate GABA signaling during different developmental stages. Significance: This is the first systematic study of GABA metabolism in Dictyostelium discoideum and broadens our knowledge of the evolution and function of GABA metabolism.

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“…Removing Dictyostelium cells from growth medium and suspending them in nonnutrient buffer results in a growth-todifferentiation transition (GDT) in which most genes expressed in the growth phase are turned off and the early developmental genes are turned on (4,7). One of the genes that is rapidly turned off, impA, is found on chromosome 4 adjacent to dia1, a gene which is expressed within an hour of GDT (3).…”

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confidence: 99%

cis -Acting Site Controlling Bidirectional Transcription at the Growth-Differentiation Transition in Dictyostelium discoideum

2006

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A pair of adjacent genes, impA and dia1, are divergently transcribed but expressed at different stages in the life cycle of Dictyostelium discoideum. The intervening 654-bp region carries cis-acting regions that are essential for transcription in both directions as well as repression of dia1 in growing cells. We have focused on a 112-bp region proximal to dia1 that is essential for bidirectional transcription. Analyses of a set of internal deletions showed that the sequence between positions 80 and 97 (TTTGAATTTTTTGAATTT) is critical and that bases outside this region are dispensable. Site-directed mutations within this critical region confirmed the importance of this sequence for transcription both to the right and to the left. However, insertions of either 6 or 24 Ts into the run of 6 Ts separating the repeated GAA sequence had little effect on the functioning of the site in either direction, suggesting that factors recognize the half-sites TTGAATT separately. Inversion of the bases between positions 80 and 97 greatly reduced expression in both directions, indicating that orientation is critical for expression of both the nearby impA gene and the distal dia1 gene, which is more than 500 bp away. Comparison of 38 mutant constructs with multiple random variations in the region indicated that transcription factors may bind to a range of related sequences and still retain function. All functional constructs directed transcription both leftward and rightward, while all nonfunctional constructs were impaired for transcription in both directions. It appears that the same transcription complex controls transcription of both impA and dia1.

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Genome-Wide Expression Analyses of Gene Regulation during Early Development of Dictyostelium discoideum

Cited by 86 publications

References 42 publications

Constitutively Active G Protein-coupled Receptor Mutants BlockDictyosteliumDevelopment

Constitutively Active G Protein-coupled Receptor Mutants BlockDictyosteliumDevelopment

Systematic Analysis of γ-Aminobutyric Acid (GABA) Metabolism and Function in the Social Amoeba Dictyostelium discoideum

cis -Acting Site Controlling Bidirectional Transcription at the Growth-Differentiation Transition in Dictyostelium discoideum

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