Control of Aggregation in Dictyostelium discoideum by an External Periodic Pulse of Cyclic Adenosine Monophosphate

Science ◽  
1972 ◽  
Vol 175 (4019) ◽  
pp. 333-335 ◽  
Author(s):  
A. Robertson ◽  
D. J. Drage ◽  
M. H. Cohen
Keyword(s):  
Dictyostelium Discoideum ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Periodic Pulse

scholarly journals Cooperation of the haves and the have-nots

2017 ◽  
Author(s):  
Kaumudi H Prabhakara ◽  
Albert J Bae ◽  
Eberhard Bodenschatz
Keyword(s):  
Social Behavior ◽  
Dictyostelium Discoideum ◽  
Large Scale ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Divalent Ions ◽  
Complementary Resources ◽  
Degradation Rates ◽  
Chemical Messenger ◽  
Cell To Cell Variability

AbstractUpon starvation, Dictyostelium discoideum (D.d.) exhibit social behavior mediated by the chemical messenger cyclic adenosine monophosphate (cAMP). Large scale cAMP waves synchronize the population of starving cells and enable them to aggregate and form a multi-cellular organism. Here, we explore the effect of cell-to-cell variability in the production of cAMP on aggregation. We create a mixture of extreme cell-to-cell variability by mixing a few cells that produce cAMP (haves) with a majority of mutants that cannot produce cAMP (have-nots). Surprisingly, such mixtures aggregate, although each population on its own cannot aggregate. We show that (1) a lack of divalent ions kills the haves at low densities and (2) the have-nots supply the cAMP degrading enzyme, phosphodiesterase, which, in the presence of divalent ions, enables the mixture to aggregate. Our results suggest that a range of degradation rates induces optimal aggregation. The haves and the have-nots cooperate by sharing complementary resources.

scholarly journals Extracellular vesicles direct migration by synthesizing and releasing chemotactic signals

2018 ◽  
Vol 217 (8) ◽  
pp. 2891-2910 ◽  
Author(s):  
Paul W. Kriebel ◽  
Ritankar Majumdar ◽  
Lisa M. Jenkins ◽  
Hiroshi Senoo ◽  
Weiye Wang ◽  
...  
Keyword(s):  
Adenylyl Cyclase ◽  
Dictyostelium Discoideum ◽  
Extracellular Vesicles ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Multivesicular Bodies ◽  
Signal Relay

Chemotactic signals are relayed to neighboring cells through the secretion of additional chemoattractants. We previously showed in Dictyostelium discoideum that the adenylyl cyclase A, which synthesizes the chemoattractant cyclic adenosine monophosphate (cAMP), is present in the intraluminal vesicles of multivesicular bodies (MVBs) that coalesce at the back of cells. Using ultrastructural reconstructions, we now show that ACA-containing MVBs release their contents to attract neighboring cells. We show that the released vesicles are capable of directing migration and streaming and are central to chemotactic signal relay. We demonstrate that the released vesicles not only contain cAMP but also can actively synthesize and release cAMP to promote chemotaxis. Through proteomic, pharmacological, and genetic approaches, we determined that the vesicular cAMP is released via the ABCC8 transporter. Together, our findings show that extracellular vesicles released by D. discoideum cells are functional entities that mediate signal relay during chemotaxis and streaming.

scholarly journals Essential role of PI3-kinase and phospholipase A2 in Dictyostelium discoideum chemotaxis

2007 ◽  
Vol 177 (5) ◽  
pp. 809-816 ◽  
Author(s):  
Peter J.M. van Haastert ◽  
Ineke Keizer-Gunnink ◽  
Arjan Kortholt
Keyword(s):  
Phospholipase A2 ◽  
Dictyostelium Discoideum ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Pi3 Kinase ◽  
Ip3 Receptor ◽  
Second Messenger Systems ◽  
Phosphatase And Tensin Homologue ◽  
Mutant Cells

Chemotaxis toward different cyclic adenosine monophosphate (cAMP) concentrations was tested in Dictyostelium discoideum cell lines with deletion of specific genes together with drugs to inhibit one or all combinations of the second-messenger systems PI3-kinase, phospholipase C (PLC), phospholipase A2 (PLA2), and cytosolic Ca2+. The results show that inhibition of either PI3-kinase or PLA2 inhibits chemotaxis in shallow cAMP gradients, whereas both enzymes must be inhibited to prevent chemotaxis in steep cAMP gradients, suggesting that PI3-kinase and PLA2 are two redundant mediators of chemotaxis. Mutant cells lacking PLC activity have normal chemotaxis; however, additional inhibition of PLA2 completely blocks chemotaxis, whereas inhibition of PI3-kinase has no effect, suggesting that all chemotaxis in plc-null cells is mediated by PLA2. Cells with deletion of the IP3 receptor have the opposite phenotype: chemotaxis is completely dependent on PI3-kinase and insensitive to PLA2 inhibitors. This suggest that PI3-kinase–mediated chemotaxis is regulated by PLC, probably through controlling PIP2 levels and phosphatase and tensin homologue (PTEN) activity, whereas chemotaxis mediated by PLA2 appears to be controlled by intracellular Ca2+.

scholarly journals Inhibiting Neddylation with MLN4924 Suppresses Growth and Delays Multicellular Development in Dictyostelium discoideum

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 482
Author(s):  
Robert J. Huber ◽  
William D. Kim ◽  
Sabateeshan Mathavarajah
Keyword(s):  
Dictyostelium Discoideum ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Biological Processes ◽  
Neural Precursor Cell ◽  
Post Translational Modification ◽  
Fruiting Body Formation ◽  
Multicellular Development ◽  
Cellular Processes ◽  
The Social

Neddylation is a post-translational modification that is essential for a variety of cellular processes and is linked to many human diseases including cancer, neurodegeneration, and autoimmune disorders. Neddylation involves the conjugation of the ubiquitin-like modifier neural precursor cell expressed developmentally downregulated protein 8 (NEDD8) to target proteins, and has been studied extensively in various eukaryotes including fungi, plants, and metazoans. Here, we examine the biological processes influenced by neddylation in the social amoeba, Dictyostelium discoideum, using a well-established inhibitor of neddylation, MLN4924 (pevonedistat). NEDD8, and the target of MLN4924 inhibition, NEDD8-activating enzyme E1 (NAE1), are highly conserved in D. discoideum (Nedd8 and Nae1, respectively). Treatment of D. discoideum cells with MLN4924 increased the amount of free Nedd8, suggesting that MLN4924 inhibited neddylation. During growth, MLN4924 suppressed cell proliferation and folic acid-mediated chemotaxis. During multicellular development, MLN4924 inhibited cyclic adenosine monophosphate (cAMP)-mediated chemotaxis, delayed aggregation, and suppressed fruiting body formation. Together, these findings indicate that neddylation plays an important role in regulating cellular and developmental events during the D. discoideum life cycle and that this organism can be used as a model system to better understand the essential roles of neddylation in eukaryotes, and consequently, its involvement in human disease.

Mechanisms of ATP to cAMP Conversion Catalyzed by the Mammalian Adenylyl Cyclase: A Role of Magnesium Coordination Shells and Proton Wires

2019 ◽  
Author(s):  
Bella Grigorenko ◽  
Igor Polyakov ◽  
Alexander Nemukhin
Keyword(s):  
Adenylyl Cyclase ◽  
Bond Cleavage ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Md Simulations ◽  
Coordination Shell ◽  
Energy Profile ◽  
One Step ◽  
Type V

<p>We report a mechanism of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP) conversion by the mammalian type V adenylyl cyclase revealed in molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) simulations. We characterize a set of computationally derived enzyme-substrate (ES) structures showing an important role of coordination shells of magnesium ions in the solvent accessible active site. Several stable six-fold coordination shells of Mg<sub>A</sub><sup>2+ </sup>are observed in MD simulations of ES complexes. In the lowest energy ES conformation, the coordination shell of Mg<sub>A</sub><sup>2+ </sup>does not include the O<sub>δ1</sub> atom of the conserved Asp440 residue. Starting from this conformation, a one-step reaction mechanism is characterized which includes proton transfer from the ribose O<sup>3'</sup>H<sup>3' </sup>group in ATP to Asp440 via a shuttling water molecule and P<sup>A</sup>-O<sup>3A</sup> bond cleavage and O<sup>3'</sup>-P<sup>A</sup> bond formation. The energy profile of this route is consistent with the observed reaction kinetics. In a higher energy ES conformation, Mg<sub>A</sub><sup>2+</sup> is bound to the O<sub>δ1</sub>(Asp440) atom as suggested in the relevant crystal structure of the protein with a substrate analog. The computed energy profile initiated by this ES is characterized by higher energy expenses to complete the reaction. Consistently with experimental data, we show that the Asp440Ala mutant of the enzyme should exhibit a reduced but retained activity. All considered reaction pathways include proton wires from the O<sup>3'</sup>H<sup>3' </sup>group via shuttling water molecules. </p>

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