Signal relay during chemotaxis

Garcia, Gene L.; Parent, Carole A.

doi:10.1111/j.1365-2818.2008.02066.x

Cited by 39 publications

(35 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other lagging-edge proteins do not localize asymmetrically in growing cells or noticeably increase polarity when overexpressed (11,21,24,60). Consistent with its role in enhancing polarity, CynA transcription is up-regulated during differentiation, with low levels in growing cells and a peak after 8 h of starvation, when cells acquire maximal polarity and aggregate into mound structures (61,62) (data are accessible at dictybase.org) (36,63,64). Although our data indicate that CynA is important for establishing polarity, other factors also mediate this process, as expected given the redundancy of the signaling and cytoskeletal networks.…”

Section: Discussionmentioning

confidence: 63%

Novel protein Callipygian defines the back of migrating cells

Swaney

Borleis

Iglesias

et al. 2015

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

View full text Add to dashboard Cite

Asymmetric protein localization is essential for cell polarity and migration. We report a novel protein, Callipygian (CynA), which localizes to the lagging edge before other proteins and becomes more tightly restricted as cells polarize; additionally, it accumulates in the cleavage furrow during cytokinesis. CynA protein that is tightly localized, or "clustered," to the cell rear is immobile, but when polarity is disrupted, it disperses throughout the membrane and responds to uniform chemoattractant stimulation by transiently localizing to the cytosol. These behaviors require a pleckstrin homology-domain membrane tether and a WD40 clustering domain, which can also direct other membrane proteins to the back. Fragments of CynA lacking the pleckstrin homology domain, which are normally found in the cytosol, localize to the lagging edge membrane when coexpressed with full-length protein, showing that CynA clustering is mediated by oligomerization. Cells lacking CynA have aberrant lateral protrusions, altered leading-edge morphology, and decreased directional persistence, whereas those overexpressing the protein display exaggerated features of polarity. Consistently, actin polymerization is inhibited at sites of CynA accumulation, thereby restricting protrusions to the opposite edge. We suggest that the mutual antagonism between CynA and regions of responsiveness creates a positive feedback loop that restricts CynA to the rear and contributes to the establishment of the cell axis.chemotaxis | polarity | asymmetry | Dictyostelium | protein localization

show abstract

Section: Discussionmentioning

confidence: 63%

Novel protein Callipygian defines the back of migrating cells

Swaney

Borleis

Iglesias

et al. 2015

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

View full text Add to dashboard Cite

show abstract

“…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%

“…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.

View full text Add to dashboard Cite

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...

show abstract

“…There are various theories about how this may work [59,70]. The cells not only respond to cAMP by moving, but can amplify detected cAMP signals resulting in a cAMP relay mechanism [22,[71][72][73]. This has been modelled extensively [74,75].…”

Section: Aggregationmentioning

confidence: 99%

Progress and perspectives in signal transduction, actin dynamics, and movement at the cell and tissue level: lessons fromDictyostelium

2016

View full text Add to dashboard Cite

Movement of cells and tissues is a basic biological process that is used in development, wound repair, the immune response to bacterial invasion, tumour formation and metastasis, and the search for food and mates. While some cell movement is random, directed movement stimulated by extracellular signals is our focus here. This involves a sequence of steps in which cells first detect extracellular chemical and/or mechanical signals via membrane receptors that activate signal transduction cascades and produce intracellular signals. These intracellular signals control the motile machinery of the cell and thereby determine the spatial localization of the sites of force generation needed to produce directed motion. Understanding how force generation within cells and mechanical interactions with their surroundings, including other cells, are controlled in space and time to produce cell-level movement is a major challenge, and involves many issues that are amenable to mathematical modelling.

show abstract

Signal relay during chemotaxis

Cited by 39 publications

References 64 publications

Novel protein Callipygian defines the back of migrating cells

Novel protein Callipygian defines the back of migrating cells

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

Progress and perspectives in signal transduction, actin dynamics, and movement at the cell and tissue level: lessons fromDictyostelium

Contact Info

Product

Resources

About