Analysis of chemotaxis in Dictyostelium (original) (raw)
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Cellular and molecular life sciences : CMLS, 2014
Chemotaxis, or directed migration of cells along a chemical gradient, is a highly coordinated process that involves gradient sensing, motility, and polarity. Most of our understanding of chemotaxis comes from studies of cells undergoing amoeboid-type migration, in particular the social amoeba Dictyostelium discoideum and leukocytes. In these amoeboid cells the molecular events leading to directed migration can be conceptually divided into four interacting networks: receptor/G protein, signal transduction, cytoskeleton, and polarity. The signal transduction network occupies a central position in this scheme as it receives direct input from the receptor/G protein network, as well as feedback from the cytoskeletal and polarity networks. Multiple overlapping modules within the signal transduction network transmit the signals to the actin cytoskeleton network leading to biased pseudopod protrusion in the direction of the gradient. The overall architecture of the networks, as well as the ...
Signaling pathways mediating chemotaxis in the social amoeba, Dictyostelium discoideum
European Journal of Cell Biology, 2006
Chemotaxis, or cell migration guided by chemical cues, is critical for a multitude of biological processes in a diverse array of organisms. Dictyostelium discoideum amoebae rely on chemotaxis to find food and to survive starvation conditions, and we have taken advantage of this system to study the molecular regulation of this vital cell behavior. Previous work has identified phosphoinositide signaling as one mechanism which may contribute to directional sensing and actin polymerization during chemotaxis; a mechanism which is conserved in mammalian neutrophils. In this review, we will discuss recent data on genes and pathways governing directional sensing and actin polymerization, with a particular emphasis on contributions from our laboratory.
Journal of Cell Science, 2008
The directed cell migration towards a chemotactic source, chemotaxis, involves three complex and interrelated processes: directional sensing, cell polarization and motility. Directional sensing allows migrating eukaryotic cells to chemotax in extremely shallow gradients (<2% across the cell body) of the chemoattractant. Although directional sensing has been observed as spatially restricted responses along the plasma membrane, our understanding of the `compass' of the cell that controls the gradient-induced translocation of proteins during chemotactic movements is still largely lacking. Until now, the dynamical behaviour and mobility of the chemoattractant-receptor molecule has been neglected in models describing the directional sensing mechanisms. Here, we show by single-molecule microscopy an agonist-induced increase in the mobile fraction of cAMP-receptor at the leading edge of chemotacting Dictyostelium discoideum cells. The onset of receptor mobility was correlated to the...
Highlighting the role of Ras and Rap during Dictyostelium chemotaxis
Cellular Signalling, 2008
Chemotaxis, the directional movement towards a chemical compound, is an essential property of many cells and has been linked to the development and progression of many diseases. Eukaryotic chemotaxis is a complex process involving gradient sensing, cell polarity, remodelling of the cytoskeleton and signal relay. Recent studies in the model organism Dictyostelium discoideum have shown that chemotaxis does not depend on a single molecular mechanism, but rather depends on several interconnecting pathways. Surprisingly, small G-proteins appear to play essential roles in all these pathways. This review will summarize the role of small G-proteins in Dictyostelium, particularly highlighting the function of the Ras subfamily in chemotaxis. address: P.J.M.van.Haastert@rug.nl (P.J.M. van Haastert).
EMBO reports, 2011
Central to chemotaxis is the molecular mechanism by which cells exhibit directed movement in shallow gradients of a chemoattractant. We used Dictyostelium mutants to investigate the minimal requirements for chemotaxis, and identified a basal signalling module providing activation of Ras at the leading edge, which is sufficient for chemotaxis. The signalling enzymes PI3K, TorC2, PLA2 and sGC are not required for Ras activation and chemotaxis to folate or to steep gradients of cAMP, but they provide a memory of direction and improved orientation of the cell, which together increase the sensitivity about 150-fold for chemotaxis in shallow cAMP gradients.
Journal of muscle research and …, 2002
In the natural aggregation process, Dictyostelium amoebae relay the cAMP signal outwardly through the cell population as symmetric, nondissipating waves. Each cell in turn responds in a specific manner to the different phases of the wave. In the front of each wave, each cell experiences an increasing temporal gradient and positive spatial gradient of cAMP; at the peak of each wave, each cell experiences a cAMP concentration inhibitory to locomotion; and in the back of each wave, each cell experiences a decreasing temporal and negative spatial gradient of cAMP. Protocols are described to analyze the basic motile behavior of mutant cells in the absence of a chemotactic signal, and to test the responsiveness of mutant cells to the individual temporal, spatial and concentration components of a natural wave. The results of such an analysis can then be used to develop realistic models of cell motility and chemotaxis. Examples are described in which this contextual framework has been applied to mutant cell lines. The results of these mutant studies result in a model in which independent parallel regulatory pathways emanating from different phases of the wave effect different phase-specific behaviors.
Microarray phenotyping in Dictyostelium reveals a regulon of chemotaxis genes
Bioinformatics, 2005
Motivation: Coordinate regulation of gene expression can provide information on gene function. To begin a large-scale analysis of Dictyostelium gene function, we clustered genes based on their expression in wild-type and mutant strains and analyzed their functions. Results: We found 17 modes of wild-type gene expression and refined them into 57 submodes considering mutant data. Annotation analyses revealed correlations between co-expression and function and an unexpected correlation between expression and function of genes involved in various aspects of chemotaxis . Co-regulation of chemotaxis genes was also found in published data from neutrophils. To test the predictive power of the analysis, we examined the phenotypes of mutations in seven co-regulated genes that had no published role in chemotaxis. Six mutants exhibited chemotaxis defects, supporting the idea that function can be inferred from co-expression. The clustering and annotation analyses provide a public resource for Dictyostelium functional genomics.
Local and spatially coordinated movements in Dictyostelium discoideum amoebae during chemotaxis
Cell, 1982
We have studied chemotaxis by individual Dictyostelium discoideum amoebae using strong, local gradients of the chemoattractant cyclic AMP. Gradients were provided by diffusion of cyclic AMP from a microneedle, which could be positioned at various points around the cell. Responses to changes in the gradient indicate how the cell is structurally organized for chemotactic movement. There is a polarity in the responsiveness of the surface to stimulation by cyclic AMP along the length of the amoeba. Furthermore, two aspects of chemotactic movement can be distinguished. The first response to cyclic AMP is a locally generated extension of a hyaline pseudopod from the region of the surface nearest the stimulus. The second response, the flow of cytoplasm in the direction of the stimulus, is coordinated and separate from the first response. The coordination appears to depend on the nucleus or on the microtubule-organizing center.
Annual Review of Biophysics, 2010
Chemotaxis, the directed migration of cells in chemical gradients, is a vital process in normal physiology and in the pathogenesis of many diseases. Chemotactic cells display motility, directional sensing, and polarity. Motility refers to the random extension of pseudopodia, which may be driven by spontaneous actin waves that propagate through the cytoskeleton. Directional sensing is mediated by a system that detects temporal and spatial stimuli and biases motility toward the gradient. Polarity gives cells morphologically and functionally distinct leading and lagging edges by relocating proteins or their activities selectively to the poles. By exploiting the genetic advantages of Dictyostelium, investigators are working out the complex network of interactions between the proteins that have been implicated in the chemotactic processes of motility, directional sensing, and polarity.
Dictyostelium PAKc Is Required for Proper Chemotaxis
Molecular Biology of the Cell, 2004
We have identified a new Dictyostelium p21-activated protein kinase, PAKc, that we demonstrate to be required for proper chemotaxis. PAKc contains a Rac-GTPase binding (CRIB) and autoinhibitory domain, a PAK-related kinase domain, an N-terminal phosphatidylinositol binding domain, and a C-terminal extension related to the G␥ binding domain of Saccharomyces cerevisiae Ste20, the latter two domains being required for PAKc transient localization to the plasma membrane. In response to chemoattractant stimulation, PAKc kinase activity is rapidly and transiently activated, with activity levels peaking at ϳ10 s. pakc null cells exhibit a loss of polarity and produce multiple lateral pseudopodia when placed in a chemoattractant gradient. PAKc preferentially binds the Dictyostelium Rac protein RacB, and point mutations in the conserved CRIB that abrogate this binding result in misregulated kinase activation and chemotaxis defects. We also demonstrate that a null mutation lacking the PAK family member myosin I heavy chain kinase (MIHCK) shows mild chemotaxis defects, including the formation of lateral pseudopodia. A null strain lacking both PAKc and the PAK family member MIHCK exhibits severe loss of cell movement, suggesting that PAKc and MIHCK may cooperate to regulate a common chemotaxis pathway. ‡ Present address: