Collective cell migration requires vesicular trafficking for chemoattractant delivery at the trailing edge

Kriebel, Paul W.; Barr, Valarie A.; Rericha, Erin; Zhang, Guofeng; Parent, Carole A.

doi:10.1083/jcb.200808105

Cited by 96 publications

(125 citation statements)

References 61 publications

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“…13, upper row, left) a trail of secreted ACA vesicles was observed. This behavior is in agreement with the localization and secretion of ACA vesicles in wild-type cells (58). In contrast, ACA-YFP in cells expressing F-Y/A-actin (Fig.…”

Section: Cell Numbersupporting

confidence: 73%

Expression of Y53A-Actin in Dictyostelium Disrupts the Cytoskeleton and Inhibits Intracellular and Intercellular Chemotactic Signaling

Shu

Liu

Kriebel

et al. 2010

Journal of Biological Chemistry

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We showed previously that phosphorylation of Tyr 53 , or its mutation to Ala, inhibits actin polymerization in vitro with formation of aggregates of short filaments, and that expression of Y53A-actin in Dictyostelium blocks differentiation and development at the mound stage (Liu, X., Shu, S. We now show that expression of Y53A-actin, which does not affect cell growth, phagocytosis, or pinocytosis, inhibits the formation of head-to-tail cell streams during cAMP-induced aggregation, although individual amoebae chemotax normally. We show that expression of Y53A-actin causes a 50% reduction of cell surface cAMP receptors, and inhibits cAMPinduced increases in adenylyl cyclase A activity, phosphorylation of ERK2, and actin polymerization. Trafficking of vesicles containing adenylyl cyclase A to the rear of the cell and secretion of the ACA vesicles are also inhibited. The actin cytoskeleton of cells expressing Y53A-actin is characterized by numerous short filaments, and bundled and aggregated filaments similar to the structures formed by copolymerization of purified Y53A-actin and wild-type actin in vitro. This disorganized actin cytoskeleton may be responsible for the inhibition of intracellular and intercellular cAMP signaling in cells expressing F-Y53A-actin.

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Section: Cell Numbersupporting

confidence: 73%

Expression of Y53A-Actin in Dictyostelium Disrupts the Cytoskeleton and Inhibits Intracellular and Intercellular Chemotactic Signaling

Shu

Liu

Kriebel

et al. 2010

Journal of Biological Chemistry

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“…Although both models are capable of reproducing many features of Dictyostelium aggregation, including the propagation of cAMP waves in characteristic spirals and the formation of stream-like aggregates, they are not perfect. In previous work, we have proposed that the secretion of cAMP is spatially restricted (Kriebel et al, 2003(Kriebel et al, , 2008. We now show that only the secreted form of PdsA can degrade the external cAMP signal and that the addition of a uniform bolus of PdsA does not lead to the formation of highly branched, head-to-tail lines characteristic of WT streaming.…”

Section: Discussionmentioning

confidence: 52%

“…Interestingly, as cells form aggregates, they acquire the ability to migrate in groups by aligning in a head-to-tail manner, forming characteristic streams. We have previously shown that the ability of cells to stream depends on the enrichment of ACA-containing vesicles at the back of migrating cells (Kriebel et al, 2003(Kriebel et al, , 2008. We propose that the formation of head-to-tail arrays is regulated by the specific release of cAMP from vesicles at the back of cells.…”

Section: Introductionmentioning

confidence: 82%

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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“…In general, a response to a step stimulus may not necessarily have the same propensity as that for a slowly varying stimulus. Moreover, directional migration is induced by a traveling-wave stimulus (17,18) and thus may affect the cAMP relay owing to a large overlap in the signal transduction network (16,31,32). To test relevance of the fold-change response property for natural cAMP wave, we used a microfluidics lighthouse (33)-a gradient-generating platform capable of delivering traveling-wave stimulus of various amplitude, frequencies, and speed.…”

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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Collective cell migration requires vesicular trafficking for chemoattractant delivery at the trailing edge

Cited by 96 publications

References 61 publications

Expression of Y53A-Actin in Dictyostelium Disrupts the Cytoskeleton and Inhibits Intracellular and Intercellular Chemotactic Signaling

Expression of Y53A-Actin in Dictyostelium Disrupts the Cytoskeleton and Inhibits Intracellular and Intercellular Chemotactic Signaling

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

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

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