Oscillatory signaling and network responses during the development of Dictyostelium discoideum

McMains, Vanessa C.; Liao, Xin‐Hua; Kimmel, Alan R.

doi:10.1016/j.arr.2008.04.003

Cited by 46 publications

(86 citation statements)

References 94 publications

(137 reference statements)

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“…The cAMP relay response is mediated by complex signaling cascades downstream of G-protein-coupled receptors that are yet to be fully revealed (31,35). Binding of extracellular cAMP to the receptor activates small GTPase Ras, which then activates phosphoinositide 3-kinase (PI3K) to elevate phosphatidylinositol-(3,4,5)-triphosphate (PIP 3 ) at the plasma membrane (36).…”

Section: Resultsmentioning

confidence: 99%

Fold-change detection and scale invariance of cell–cell signaling in social amoeba

Kamino

Kondo

Nakajima

et al. 2017

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

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Cell-cell signaling is subject to variability in the extracellular volume, cell number, and dilution that potentially increase uncertainty in the absolute concentrations of the extracellular signaling molecules. To direct cell aggregation, the social amoebae Dictyostelium discoideum collectively give rise to oscillations and waves of cyclic adenosine 3′,5′-monophosphate (cAMP) under a wide range of cell density. To date, the systems-level mechanism underlying the robustness is unclear. By using quantitative live-cell imaging, here we show that the magnitude of the cAMP relay response of individual cells is determined by fold change in the extracellular cAMP concentrations. The range of cell density and exogenous cAMP concentrations that support oscillations at the population level agrees well with conditions that support a large fold-change-dependent response at the singlecell level. Mathematical analysis suggests that invariance of the oscillations to density transformation is a natural outcome of combining secrete-and-sense systems with a fold-change detection mechanism.fold-change detection | oscillations | collective behavior | Dictyostelium | robustness C ell-cell signaling lies at the basis of development and maintenance of multicellular forms of life. Extracellular signals are often subject to greater fluctuations in the size of extracellular space and the number of cells (Fig. 1A), not to mention nonspecific binding to other molecules, degradation, and dilution. These factors introduce an uncertainty to the detectable number of extracellular ligand molecules, thus posing a threat to the fidelity of cell-cell communication. One of the means by which cells could cope with such uncertainties is to base their behavioral decisions on temporal changes in the extracellular signals. Persistent stimuli are often ignored while their changes in time elicit transient responses-a property collectively called adaptation (1-3). Recent studies have highlighted cellular response whose magnitude appears to be dictated by the fold change in the input stimuli-a property referred to as "fold-change detection" (FCD) (4, 5). In bacterial chemotaxis, cells respond adaptively to a fold change in chemoattractant concentration (6) so that their search patterns depend only on the spatial profiles of the chemoattractant irrespective of its absolute level. Fold-change dependence is also implied in eukaryotic chemotactic response (7, 8) as well as cell fate control and gene regulation in Xenopus embryo (9), Drosophila imaginal disk (10), and mammalian cells (11). These studies have shed light on the role of FCD for a simple unidirectional signal transduction from an extracellular ligand-receptor interaction (input) to a cellular response (output). However, cell-cell signaling and multicellular systems as a whole often use secretion and sensing of the same molecules (12), whereby the output is fed back to the responding cell itself in addition to the neighboring cells, thus forming a complex bidirectional signal transduction system. Th...

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Section: Resultsmentioning

confidence: 99%

Fold-change detection and scale invariance of cell–cell signaling in social amoeba

Kamino

Kondo

Nakajima

et al. 2017

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

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“…On the onset of starvation conditions, the cells enter a developmental program that leads to the aggregation of a group of up to 100,000 cells that eventually form a multicelluar structure. The formation of the aggregate is mediated by the cyclic nucleotide cAMP, which serves as a chemoattractant (Saran et al, 2002;Garcia and Parent, 2008;McMains et al, 2008). Soon after the onset of starvation, development is initiated by the expression of the adenylyl cyclase A (ACA) and the G protein-coupled cAMP receptor 1 (cAR1) as well as other genes involved in intracellular signaling and sensing of external cAMP (Devreotes, 1994;Parent and Devreotes, 1996;Aubry and Firtel, 1999;Weeks, 2000).…”

Section: Introductionmentioning

confidence: 99%

The Group Migration of Dictyostelium Cells Is Regulated by Extracellular Chemoattractant Degradation

Garcia

Rericha

Heger

et al. 2009

MBoC

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Starvation of Dictyostelium induces a developmental program in which cells form an aggregate that eventually differentiates into a multicellular structure. The aggregate formation is mediated by directional migration of individual cells that quickly transition to group migration in which cells align in a head-to-tail manner to form streams. Cyclic AMP acts as a chemoattractant and its production, secretion, and degradation are highly regulated. A key protein is the extracellular phosphodiesterase PdsA. In this study we examine the role and localization of PdsA during chemotaxis and streaming. We find that pdsA ؊ cells respond chemotactically to a narrower range of chemoattractant concentrations compared with wild-type (WT) cells. Moreover, unlike WT cells, pdsA ؊ cells do not form streams at low cell densities and form unusual thick and transient streams at high cell densities. We find that the intracellular pool of PdsA is localized to the endoplasmic reticulum, which may provide a compartment for storage and secretion of PdsA. Because we find that cAMP synthesis is normal in cells lacking PdsA, we conclude that signal degradation regulates the external cAMP gradient field generation and that the group migration behavior of these cells is compromised even though their signaling machinery is intact. INTRODUCTIONThe process by which cells sense an attractant molecule and respond by migrating directionally toward it is called chemotaxis. Chemotaxis is essential for a variety of physiological processes in mammals as well as for the survival of lower eukaryotes. The mechanisms that regulate the directed migration of neutrophils and Dictyostelium discoideum have been extensively studied previously (van Haastert and Devreotes, 2004;Bagorda et al., 2006;Friedl and Weigelin, 2008;Stephens et al., 2008). One particular challenge of these fast-moving cells is to maintain the ability to respond sensitively and rapidly to an attractant signal. Because both neutrophils and Dictyostelium cells use signal relay loops to propagate chemoattractant signals, mechanisms must be at play to maintain detectable levels of chemoattractants. Remarkably, signal degradation also seems to play an important role in the developmental processes of multicellular organisms. Migration of primordial germ cells in Drosophila and Zebrafish seems to require degradation of specific lysophospholipids in the former or chemokines in the latter to allow these cells to find their proper developmental environment (Renault and Lehmann, 2006;Minina et al., 2007). Many cell types use receptor-mediated degradation to maintain detectable levels of chemoattractants. In this context, cells internalize the bound receptor and as part of the receptor recycling pathway the ligand is released for degradation (Minina et al., 2007;Boldajipour et al., 2008;Borroni et al., 2008;Scola et al., 2008). Alternatively, extracellular enzymes can specifically degrade the extracellular signaling molecules, allowing the sensing machinery to go back to basal levels and retain high se...

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“…Although part of the synthesized cAMP remains inside cells to activate PKA and regulate gene expression, the majority of it is rapidly secreted (5-7). The secreted cAMP binds to cAR1 and, in an autocrine and paracrine amplification step, results in the production and secretion of more cAMP (2,3). For a spatially extended cell population, the stimulated release of cAMP results in propagating spiral waves of cAMP secretion, allowing neighboring cells to polarize and migrate directionally and form characteristic chains of cells called streams as they move toward an aggregation center.…”

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confidence: 99%

“…Signal transduction is important during development where the transition from single to collective cell migration is regulated by multiple external cues (1). Cell-cell communication, a process that can be manifested through the relay of external chemical signals (2,3), is critical for a wide range of developmental processes including the survival of the social amoebae Dictyostelium discoideum.…”

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confidence: 99%

Direct Biochemical Measurements of Signal Relay during Dictyostelium Development

Das

Rericha

Bagorda

et al. 2011

Journal of Biological Chemistry

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Upon starvation, individual Dictyostelium discoideum cells enter a developmental program that leads to collective migration and the formation of a multicellular organism. The process is mediated by extracellular cAMP binding to the G proteincoupled cAMP receptor 1, which initiates a signaling cascade leading to the activation of adenylyl cyclase A (ACA), the synthesis and secretion of additional cAMP, and an autocrine and paracrine activation loop. The release of cAMP allows neighboring cells to polarize and migrate directionally and form characteristic chains of cells called streams. We now report that cAMP relay can be measured biochemically by assessing ACA, ERK2, and TORC2 activities at successive time points in development after stimulating cells with subsaturating concentrations of cAMP. We also find that the activation profiles of ACA, ERK2, and TORC2 change in the course of development, with later developed cells showing a loss of sensitivity to the relayed signal. We examined mutants in PKA activity that have been associated with precocious development and find that this loss in responsiveness occurs earlier in these mutants. Remarkably, we show that this loss in sensitivity correlates with a switch in migration patterns as cells transition from streams to aggregates. We propose that as cells proceed through development, the cAMP-induced desensitization and down-regulation of cAMP receptor 1 impacts the sensitivities of chemotactic signaling cascades leading to changes in migration patterns.The directed migration of individual cells or chains or sheets of cells requires cells to transduce external cues into internal signals that regulate cytoskeletal reorganization and cell polarity. Signal transduction is important during development where the transition from single to collective cell migration is regulated by multiple external cues (1). Cell-cell communication, a process that can be manifested through the relay of external chemical signals (2, 3), is critical for a wide range of developmental processes including the survival of the social amoebae Dictyostelium discoideum.Upon starvation, Dictyostelium cells enter a developmental program leading to the transition from cells operating individually to groups of cells operating as a population. Aggregation of starving cells is controlled by signaling centers that emit periodic pulses of 3Ј-5Ј-cAMP. This process is mediated by the binding of extracellular cAMP to the G protein-coupled receptor cAR1, 3 which initiates a signaling cascade leading to, among other things, the activation of ACA (4). When ACA is first activated, rapid cAMP synthesis leads to a burst in internal cAMP levels. Although part of the synthesized cAMP remains inside cells to activate PKA and regulate gene expression, the majority of it is rapidly secreted (5-7). The secreted cAMP binds to cAR1 and, in an autocrine and paracrine amplification step, results in the production and secretion of more cAMP (2, 3). For a spatially extended cell population, the stimulated release of cAMP result...

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Oscillatory signaling and network responses during the development of Dictyostelium discoideum

Cited by 46 publications

References 94 publications

Fold-change detection and scale invariance of cell–cell signaling in social amoeba

Fold-change detection and scale invariance of cell–cell signaling in social amoeba

The Group Migration of Dictyostelium Cells Is Regulated by Extracellular Chemoattractant Degradation

Direct Biochemical Measurements of Signal Relay during Dictyostelium Development

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